121 entries found for : pr-01
Ryan Y, Harrison A, Trivett H, Hartley C, David J, Clark GC, Hiscox JA (2022) RIPpore: A novel host-derived method for the identification of ricin intoxication through oxford nanopore direct RNA sequencing. Toxins (Basel) 14(7):470. doi: 10.3390/toxins14070470 Objective: The Depurination event could be detected using Oxford Nanopore Technologies (ONT) direct RNA sequencing, detecting a change in charge in the ricin loop. Summary: Collectively, this work highlights the potential for ONT and direct RNA sequencing to detect and quantify depurination events caused by ribosome-inactivating proteins such as ricin. Usage: Saporin was added as described by Rust et al., at 100 nM [22] for 24 h. Related Products: Saporin (Cat. #PR-01) See Also:
Li Y, Ye Z, Yang H, Xu Q (2022) Tailoring combinatorial lipid nanoparticles for intracellular delivery of nucleic acids, proteins, and drugs. Acta Pharm Sin B 12(6):2624-2639. doi: 10.1016/j.apsb.2022.04.013
Objective: To highlight the recent progress in combinatorial lipid nanoparticles (LNPs) with novel structures and properties for the delivery of small- and macromolecular therapeutics.
Summary: The administration of protein/LNP negatively impacted reproduction in rats, including sperm production, estrous cyclicity and testicular and ovarian morphology, without causing any significant side effects. This non-surgical approach can be developed into a safe and convenient strategy for controlling the overproduction of pet and wildlife.
Usage: Intravenous administration of saporin loaded LNPs
Related Products: Saporin (Cat. #PR-01)
Xu L, Füredi N, Lutter C, Geenen B, Pétervári E, Balaskó M, Dénes Á, Kovács KJ, Gaszner B, Kozicz T (2022) Leptin coordinates efferent sympathetic outflow to the white adipose tissue through the midbrain centrally-projecting Edinger-Westphal nucleus in male rats. Neuropharmacology 205:108898. doi: 10.1016/j.neuropharm.2021.108898
Objective: To show that leptin bound to neurons of the Edinger-Westphal nucleus (EWcp) stimulated STAT3 phosphorylation and increases urocortin 1 (Ucn1)-production in a time-dependent manner.
Summary: EWcp/LepRb/Ucn1 neurons respond to leptin signaling as well as control white adipose tissue size and fat metabolism without altering food intake.
Usage: Ablation of EWcp leptin receptor (LepRb) positive neurons with leptin-saporin. Either unconjugated saporin (53 ng in 80 nl MQ, or Leptin-SAP (90 ng in 80 nl MQ, was injected into the rat midbrain.
Related Products: Leptin-SAP (Cat. #IT-47), Saporin (Cat. #PR-01)
Suicide nanoplasmids coding for ribosome-inactivating proteins
Mitdank H, Tröger M, Sonntag A, Shirazi NA, Woith E, Fuchs H, Kobelt D, Walther W, Weng A (2022) Suicide nanoplasmids coding for ribosome-inactivating proteins. Eur J Pharm Sci 170:106107. doi: 10.1016/j.ejps.2021.106107
Objective: To investigate the anti-proliferative activity of suicide-nanoplasmids.
Summary: In an in vivo neuroblastoma tumor model, treated mice showed a reduced tumor growth.
Usage: Design of a suicide nanoplasmid vector with saporin.
Related Products: Saporin (Cat. #PR-01)
Ujvári B, Pytel B, Márton Z, Bognár M, Kovács LÁ, Farkas J, Gaszner T, Berta G, Kecskés A, Kormos V, Farkas B, Füredi N, Gaszner B (2022) Neurodegeneration in the centrally-projecting Edinger-Westphal nucleus contributes to the non-motor symptoms of Parkinson's disease in the rat. J Neuroinflammation 19(1):31. doi: 10.1186/s12974-022-02399-w
Objective: To investigate whether neuron loss and alpha-synuclein accumulation in the urocortin 1 containing (UCN1) cells of the centrally-projecting Edinger-Westphal (EWcp) nucleus is associated with anxiety and depression-like state in the rat.
Summary: Neurodegeneration of urocortinergic EWcp contributes to the mood-related non-motor symptoms in toxic models of Parkinson's disease in the rat.
Usage: Leptin-SAP or unconjugated Saporin (0.08 μl) was injected into the EWcp area. This selective ablation of UCN1 neurons was used to validate the depression-like phenotype in rats. Behavioral, functional–morphological, biochemical and histopathological tools were used to test the motor coordination, mood status as well as morphological changes in the brain.
Related Products: Saporin (Cat. #PR-01), Leptin-SAP (Cat. #IT-47)
Converting extracellular vesicles into nanomedicine: loading and unloading of cargo
Joshi BS, Ortiz D, Zuhorn IS (2021) Converting extracellular vesicles into nanomedicine: loading and unloading of cargo. Materials Today Nano 16:100148. doi: 10.1016/j.mtnano.2021.100148
Objective: To provide a comprehensive overview of (i) methods for the loading of EVs with therapeutic cargo, (ii) methods for EV surface functionalization to direct EVs to target cells, and (iii) methods to stimulate cargo release from EVs.
Summary: Development of methodologies to offload the natural cargo of EVs and substitute it for a cargo of interest, i.e., similar to the generation of empty viral capsids, may further aid in higher loading efficiency and enhanced therapeutic effects with improved safety.
Usage: Saporin, a small (30 kDa) ribosome-inactivating protein that induces cytotoxicity by inhibiting protein synthesis,was successfully loaded into EVs by electroporation.
Related Products: Saporin (Cat. #PR-01)
See Also:
Mitochondrial aspartate regulates TNF biogenesis and autoimmune tissue inflammation.
Wu B, Zhao TV, Jin K, Hu Z, Abdel MP, Warrington KJ, Goronzy JJ, Weyand CM (2021) Mitochondrial aspartate regulates TNF biogenesis and autoimmune tissue inflammation. Nat Immunol 22(12):1551-1562. doi: 10.1038/s41590-021-01065-2
Objective: To identify a deficiency of mitochondrial aspartate production as a key abnormality in autoimmune T cells.
Summary: Shortage of mitochondrial aspartate disrupted the regeneration of the metabolic cofactor nicotinamide adenine dinucleotide (NAD), causing ADP-deribosylation of the endoplasmic reticulum (ER) sensor GRP78/BiP. Transfer of intact mitochondria into T cells as well as supplementation of exogenous aspartate rescued the mitochondria-instructed expansion of ER membranes and suppressed TNF release and rheumatoid tissue inflammation.
Usage: Immunofluorescence (Permeabilization by 0.5% Saporin)
Related Products: Saporin (Cat. #PR-01)
Microfluidic nanomaterials: From synthesis to biomedical applications.
Illath K, Kar S, Gupta P, Shinde A, Wankhar S, Tseng FG, Lim KT, Nagai M, Santra TS (2022) Microfluidic nanomaterials: From synthesis to biomedical applications. Biomaterials 280:121247. doi: 10.1016/j.biomaterials.2021.121247
Objective: To evaluate the current state of the controlled synthesis of nanomaterials using microfluidic devices.
Summary: In summary, inherent features of microfluidics enabled the controlled synthesis of biopolymer and silica nanomaterials that can easily encapsulate drugs.
Usage: Saporin was loaded quickly with nanogel of various sizes and observed that saporin loaded protein releasing depended on the density of cross-linking.
Related Products: Saporin (Cat. #PR-01)
A brief history of saporin and its contributions to neuroscience
Shramm PA, Ancheta LR, Bouajram R, Lappi DA (2021) A brief history of saporin and its contributions to neuroscience. Neuroscience 2021 Abstracts J002.11. Society for Neuroscience, Virtual.
Summary: When investigating the origins of targeted toxins (a drug, therapy, or scientific tool directed to a unique extracellular target), an appropriate place to begin is with the Nobel Prize-winning work of Paul Ehrlich and his concept of the "magic bullet." Over 100 years later, the use of targeted toxins to perform molecular neurosurgery has become a vital practice that allows researchers to observe changes in organisms after eliminating a neuronal population. A prime example of this practice is the specific targeting of cholinergic neurons in the basal forebrain to mimic Alzheimer's disease (AD). The research tool designed for this purpose is 192-IgG-Saporin, an antibody conjugated to the ribosome-inactivating protein (RIP) Saporin. Researchers have used this targeted toxin for over 30 years. A 2019 publication by Verkhratsky et al. reviews AD models and states this is the only lesion model that specifically targets cholinergic neurons. In 1983, during a quest to find the optimal payload for a targeted toxin, Fiorenzo Stirpe and colleagues discovered Saporin, a plant protein isolated from the common soapwort plant Saponaria officinalis. Unlike ricin and abrin, Saporin does not have a binding chain and cannot enter a cell on its own. Scientists have devised new ways to use Saporin to advance their research and drug development activities. Just a few examples include: 1. A novel suicide gene therapy approach that uses a vector encoding a double-stranded DNA aptamer to deliver the gene encoding Saporin, 2. Delivery of Saporin encapsulated in a nanotechnology system for development of cancer treatments, 3. A deeper understanding of the difference between pain and itch and the relevant pathways, and 4. Development of a stable epilepsy animal model that is used for screening specific treatments that will lead to micro-methods to eliminate the disease. This review will focus on Saporin as the payload delivered to cells. Targeted toxins (typically targeted by an antibody or peptide chemically linked or genetically fused) provide robust tools for neuroscience where ablation of specific neuronal populations is used to study behavior and function. Saporin is an ideal molecule because of its extreme resistance to high temperatures and denaturation, retention of catalytic activity after conjugation, and lack of a binding chain to allow entrance to the cytoplasm of cells on its own. As a result, it is one of the most studied RIPs used for its vigorousness, potency, safety, and ease of use in the laboratory. The information presented will shed light on the history of Saporin, current applications, and what the future holds for this protein in the neuroscience field.
Related Products: Saporin (Cat. #PR-01)
Chen X, Liu H, Li A, Ji S, Fei H (2021) Hydrophobicity-tuned anion responsiveness underlies endosomolytic cargo delivery mediated by amphipathic vehicle peptides. J Biol Chem 297(6):101364. doi: 10.1016/j.jbc.2021.101364
Objective: The study focuses on hydrophobicity and a structure-function strategy to evolve a template peptide for endosomolytic cargo delivery.
Summary: The peptide LP6 could dramatically promote cargo cell entry and facilitate cytosolic delivery of biomacromolecules such as saporin.
Usage: HeLa cells were treated with saporin (10, 20, 50μg/ml) in the absence (–) or presence (+) of LP6 (20μM) to confirm the cytosolic delivery ability of LP6.
Related Products: Saporin (Cat. #PR-01)
Borkowski LF, Smith CL, Keilholz AN, Nichols NL (2021) Divergent receptor utilization is necessary for phrenic long-term facilitation over the course of motor neuron loss following CTB-SAP intrapleural injections. J Neurophysiol 126(3):709-722. doi: 10.1152/jn.00236.2021Objective: The authors tested the hypothesis that phrenic long-term facilitation (pLTF) following treatment with CTB-SAP is: 1) adenosine 2A (A2A) receptor-dependent at 7d; and 2) serotonin (5-HT) receptor-dependent at 28d.
Summary: This study furthers understanding of the contribution of differential receptor activation to pLTF and its implications for breathing following respiratory motor neuron death.
Usage: Male rats received bilateral, intrapleural injections of CTB-SAP or Saporin Control (25 μg).
Related Products: CTB-SAP (Cat. #IT-14), Saporin (Cat. #PR-01)
Dai M, Nakamura S, Takahashi C, Sato M, Munetomo A, Magata F, Uenoyama Y, Tsukamura H, Matsuda F (2021) Reduction of arcuate kappa-opioid receptor-expressing cells increased luteinizing hormone pulse frequency in female rats. Endocr J 68(8):933-941. doi: 10.1507/endocrj.EJ20-0832
Summary: The number of Kiss1-expressing cells in the ARC was not affected by ARC Dyno-SAP treatment. Dynorphin-Kappa opioid receptor (KOR) signaling within the ARC seems to mediate the suppression of the frequency of pulsatile GnRH/LH release, and neurons in the hypothalamic arcuate nucleus (ARC) non-KNDy KOR neurons may be involved in the mechanism modulating GnRH/LH pulse generation.
Usage: Female rats were stereotaxically injected with Dyno-SAP (20 ng/200 nL) or unconjugated Saporin (18.6 ng/200 nL) as a control, bilaterally into the anterior and posterior ARC (total of 4 injection sites).
Related Products: Dyno-SAP (Dynorphin-SAP) (Cat. #IT-68), Saporin (Cat. #PR-01)
Medullary noradrenergic neurons mediate hemodynamic responses to osmotic and volume challenges
Marques SM, Naves LM, Silva TME, Cavalcante KVN, Alves JM, Ferreira-Neto ML, de Castro CH, Freiria-Oliveira AH, Fajemiroye JO, Gomes RM, Colombari E, Xavier CH, Pedrino GR (2021) Medullary noradrenergic neurons mediate hemodynamic responses to osmotic and volume challenges. Front Physiol 12:649535. doi: 10.3389/fphys.2021.649535Summary: The study sought to determine the role of noradrenergic neurons in hypertonic saline infusion (HSI)-induced hemodynamic recovery. Findings show that together the A1 and A2 neurons are essential to HSI-induced cardiovascular recovery in hypovolemia.
Usage: Medullary catecholaminergic neurons were lesioned by nanoinjection of Anti-DBH-SAP (0.105 ng·nl−1) into A1, A2, or both (LES A1; LES A2; or LES A1+A2, respectively). Sham rats received nanoinjections of unconjugated saporin in the same regions.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Vagotomy and insights into the microbiota-gut-brain axis
Liu Y, Forsythe P (2021) Vagotomy and insights into the microbiota-gut-brain axis. Neurosci Res 168:20-27. doi: 10.1016/j.neures.2021.04.001
Objective: To review the use of vagotomy as a tool to explore the role of the vagus nerve in gut to brain signaling.
Summary: This review article is a summary of the knowledge gained from vagotomy, a surgical procedure that involves removing part of the vagus nerve. The article discusses using CCK-SAP to specifically ablate afferent vagal nerves in the gastrointestinal tract.
Usage: The article references a study by Diepenbroek et al. that used CCK-SAP in the following dosages: In vitro: each well was treated with a different dose of saporin conjugates (0, 2.4, 24, or 240 ng) for 24 h. In vivo: An equal volume (rat: 1 µl; mouse: 0.5 µl) of CCK-SAP (250 ng/µl) or Saporin (250 ng/µl) was injected at two sites rostral and caudal to the laryngeal nerve branch.
Related Products: CCK-SAP (Cat. #IT-31), Saporin (Cat. #PR-01)
See Also:
Reciprocal interactions between osteoclasts and nociceptive sensory neurons in bone cancer pain
Andriessen AS, Donnelly CR, Ji RR (2021) Reciprocal interactions between osteoclasts and nociceptive sensory neurons in bone cancer pain. Pain Rep 6(1):e867. doi: 10.1097/PR9.0000000000000867Summary: Current pharmacotherapies available for bone cancer pain are insufficient to provide safe and efficacious pain relief. The authors discuss the mechanisms used by cancer cells within the bone tumor microenvironment (TME) to drive bone cancer pain.
Usage: Microglial ablation using Mac-1-SAP (15 μg in 8.8 μl i.t.) and Saporin control (Cat. #PR-01, 8.8 μg in 8.8 μl), is sufficient to attenuate nerve injury-induced pain in male, but not female mice.
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)
Characterization of fever and sickness behavior regulated by cytokines during infection.
Li W, Luo S, Wan C (2020) Characterization of fever and sickness behavior regulated by cytokines during infection. Behaviour 157:855-878. doi: 10.1163/1568539X-bja10028Summary: This study reviews the characterization of fever and sickness behavior regulated by cytokines during infection.
Usage: IL-1β-saporin or unconjugated Saporin as control (icv or ip, 1.75 μg) eliminated IL-1R1-expressing cells in the hippocampus and indicated these neurons mediate the function of peripheral IL-1β induced hypophagia.
Related Products: Saporin (Cat. #PR-01)
Chlorotoxin conjugated with saporin reduces viability of ML-1 thyroid cancer cells in vitro.
Rizvanovic H, Pinheiro AD, Kim K, Thomas J (2019) Chlorotoxin conjugated with saporin reduces viability of ML-1 thyroid cancer cells in vitro. bioRxiv 885483. doi: 10.1101/2019.12.20.885483
Objective: To determine whether Chlorotoxin-conjugated Saporin (CTX-SAP) would inhibit the growth of aggressive thyroid cancer cell lines expressing MMP-2.
Summary: This in vitro study demonstrated the efficacy of a CTX-SAP conjugate in reducing the viability of ML-1 thyroid cancer cells in a dose dependent manner.
Usage: There was a statistically significant reduction in cell viability with increasing concentrations of the CTX-SAP conjugate (biotinylated Chlorotoxin mixed with Streptavidin-ZAP). The cell viability of ML-1 cells was decreased by 49.77% with the treatment of 600 nM of CTX-SAP (F=44.24). Unconjugated Chlorotoxin or Saporin had no significant effect on cell viability a using similar assay.
Related Products: Streptavidin-ZAP (Cat. #IT-27), , Saporin (Cat. #PR-01), Chlorotoxin-SAP (Cat. #IT-86)
Lesions of the patch compartment of dorsolateral striatum disrupt stimulus-response learning.
Jenrette TA, Logue JB, Horner KA (2019) Lesions of the patch compartment of dorsolateral striatum disrupt stimulus-response learning. Neuroscience 415:161-172. doi: 10.1016/j.neuroscience.2019.07.033Objective: To investigate whether enhanced activation of the patch compartment contributes to habitual behavior.
Summary: The dorsolateral patch compartment may mediate habit formation by altering information flow through basal ganglia circuits.
Usage: A volume of 2 ul of Dermorphin-SAP (17 ng/ul or an equivalent amount of unconjugated SAP (as a control) was infused bilaterally, at a rate of 0.5 ul/min.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Saporin (Cat. #PR-01)
Interleukin-1 reduces food intake and body weight in rat by acting in the arcuate hypothalamus
Chaskiel L, Bristow AD, Bluthé RM, Dantzer R, Blomqvist A, Konsman JP (2019) Interleukin-1 reduces food intake and body weight in rat by acting in the arcuate hypothalamus. Brain Behav Immun 81:560-573. doi: 10.1016/j.bbi.2019.07.017Summary: The authors tested the hypothesis that IL-1R1 expressing cells in the ARH mediate IL-1β and/or LPS-induced hypophagia in the rat.
Related Products: Saporin (Cat. #PR-01)
Pinto LG, Souza GR, Kusuda R, Lopes AH, Sant'Anna MB, Cunha FQ, Ferreira SH, Cunha TM (2019) Non-peptidergic nociceptive neurons are essential for mechanical inflammatory hypersensitivity in mice. Mol Neurobiol 56(8):5715-5728. doi: 10.1007/s12035-019-1494-5
Objective: To determine the role of non-peptidergic nociceptors in mediating mechanical inflammatory hypersensitivity in mice.
Summary: rIB4-SAP oblates non-peptidergic neurons as displayed by the decrease of purinoceptor 3. The depletion of these neurons inhibited the mechanical inflammatory sensitivity induced by GDMF and carrageenan, but not by other expected factors such as nerve growth factor implying the role of this subset of neurons to be one of mediation as opposed to direct nociception.
Usage: IB4-SAP (0.16–3.2 μg/5 μl, i.t.), unconjugated Saporin (as control, 1.8 μg/5 μl, i.t.), or saline (vehicle, 5 μl/i.t.) were injected into the subarachnoid space on the midline between the L5 and L6 vertebrae.
Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)
Identification of lineage-specific markers for therapeutic targeting of mast cells.
Plum T (2019) Identification of lineage-specific markers for therapeutic targeting of mast cells. Ruperto-Carola University of Heidelberg, Germany Thesis. doi: 10.11588/heidok.00023555Usage: Mice were injected i.v. with either 100 µg of 1:1 molar mixture of biotinylated CD63 antibody and Streptavidin-ZAP (60 µg mAb + 40 µg SAP) or with 40 µg SAP alone. All injections were performed in 200 µl PBS.
Related Products: Streptavidin-ZAP (Cat. #IT-27), Saporin (Cat. #PR-01)
Saika F, Kiguchi N, Matsuzaki S, Kobayashi D, Kishioka S (2019) Inflammatory macrophages in the sciatic nerves facilitate neuropathic pain associated with type 2 diabetes mellitus. J Pharmacol Exp Ther 368(3):535-544. doi: 10.1124/jpet.118.252668Objective: To determine whether inflammatory macrophages contribute to neuropathic pain associated with type 2 diabetes-mellitus (T2DM).
Summary: Inhibitory agents for macrophage-driven neuroinflammation could be potential candidates for novel pharmacotherapy against intractable neuropathic pain.
Usage: Injections of Mac-1-SAP or unconjugated Saporin (10 μl) were administered 3 times every 2 days. Perineural administration of Mac-1-SAP improved high-fat diet (HFD)-induced mechanical allodynia and the accumulation of F4/80+ macrophages and the upregulation of inflammatory mediators in the SCN after HFD-feeding.
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)
Microglial pannexin-1 channel activation is a spinal determinant of joint pain
Mousseau M, Burma NE, Lee KY, Leduc-Pessah H, Kwok CHT, Reid AR, O’Brien M, Sagalajev B, Stratton JA, Patrick N, Stemkowski PL, Biernaskie J, Zamponi GW, Salo P, McDougall JJ, Prescott SA, Matyas JR, Trang T (2018) Microglial pannexin-1 channel activation is a spinal determinant of joint pain. Sci Adv 4:1-12. doi: 10.1126/sciadv.aas9846Objective: To identify therapeutic targets for alleviating mechnical allodynia, a sign/symptom of arthritis.
Summary: The pannexin-1 (Panx1) channel is validated as a target; blockade of P2X7 receptors or ablation of spinal microglia prevented and reversed mechanical allodynia.
Usage: Mac-1-SAP and unconjugated Saporin (15 mg per intrathecal injection on days 0, 1, and 2). The specific depletion of spinal lumbar microglia attenuated the development of MIA-induced hypersensitivity indicating that spinal microglia causally contribute to the development of mechanical allodynia. By contrast, intrathecal injection of Control (unconjugated Saporin) did not alter the development of MIA-induced mechanical allodynia.
Related Products: Mac-1-SAP rat (Cat. #IT-33), Saporin (Cat. #PR-01)
Tan HL, Yong C, Tan BZ, Fong WJ, Padmanabhan J, Chin A, Ding V, Lau A, Zheng L, Bi X, Yang Y, Choo A (2018) Conservation of oncofetal antigens on human embryonic stem cells enables discovery of monoclonal antibodies against cancer. Sci Rep 8:11608. doi: 10.1038/s41598-018-30070-z
Objective: To identify and characterize an antibody raised using human embryonic stem cells with potential as a cancer therapeutic.
Summary: Antibody A19 not only binds to undifferentiated hESCs by flow cytometry, it also reacts with ovarian and breast cancer cell lines with low or no binding to normal cells.
Usage: in vitro - Number of viable cells treated showed a decrease in cell number (Hum-ZAP mixed with A19; Streptavidin-ZAP mixed with biotinylated A19). To determine if there were off-target effects, Hum-ZAP and chA19 were incubated with a non-binding cell line OVCAR10; no apparent cytotoxicity was observed. invivo - 5 x 106 SKOV3 cells were implanted s.c. in NUDE mice and Biotinylated A19-Streptavidin-ZAP (ADC), administered ip. The controls were free Saporin and naked A19. By the end of 10 weeks, mice administered with the ADC saw a 60% reduction in tumor size compared to control groups.
Related Products: Hum-ZAP (Cat. #IT-22), Streptavidin-ZAP (Cat. #IT-27), Saporin (Cat. #PR-01)
Naves LM, Marques SM, Mourão AA, Fajemiroye JO, Xavier CH, de Castro CH, Rebelo ACS, Rosa DA, Gomes RM, Colombari E, Pedrino GR (2018) Involvement of median preoptic nucleus and medullary noradrenergic neurons in cardiovascular and sympathetic responses of hemorrhagic rats. Sci Rep 8:11276. doi: 10.1038/s41598-018-29310-z
Objective: To evaluate the involvement of median preoptic nucleus (MnPO) and medullary noradrenergic neurons (A1 and A2) in HSS-induced cardiovascular and sympathetic responses in hemorrhagic rats.
Summary: The recovery of MAP and HSS-induced sympathoinhibition in hemorrhaged rats depend on intact neural projections from A1 and A2 to MnPO.
Usage: In order to achieve A1 and/or A2 neuronal lesions, Anti-DBH-SAP (100 nL, 0.105 ng·nL−1 ) was nanoinjected into the CVLM and NTS region, respectively. In sham groups, the equimolar of Saporin (100 nL, 0.022 ng·nL−1 ) was nanoinjected into the same site.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Gut vagal sensory signaling regulates hippocampus function through multi-order pathways.
Suarez AN, Hsu TM, Liu CM, Noble EE, Cortella AM, Nakamoto EM, Hahn JD, de Lartigue G, Kanoski SE (2018) Gut vagal sensory signaling regulates hippocampus function through multi-order pathways. Nat Commun 9(1):2181. doi: 10.1038/s41467-018-04639-1Objective: To determine the endogenous relevance of GIderived vagal HPC communication.
Summary: Endogenous derived vagal sensory signaling promotes HPC-dependent memory function via a multi-order brainstem–septal pathway, thereby identifying a previously unknown role for the gut–brain axis in memory control.
Usage: A 1-µl volume of CCK-SAP (250 ng/µl) or control Saporin (250 ng/µl) was injected at two sites: 0.5 µl rostral and 0.5 µl caudal to the laryngeal nerve branch.
Related Products: CCK-SAP (Cat. #IT-31), Saporin (Cat. #PR-01)
Patrone LGA, Biancardi V, Marques DA, Bícego KC, Gargaglioni LH (2018) Brainstem catecholaminergic neurones and breathing control during postnatal development in male and female rats. J Physiol 596(15):3299-3325. doi: 10.1113/JP275731
Objective: To determine the role of the brainstem CA system in ventilatory control under normocapnic and hypercapnic conditions during different phases of development (P7-8, P14-15 and P20-21) in male and female Wistar rats.
Summary: Brainstem CA neurones produce a tonic inhibitory drive that affects breathing frequency in P7-8 rats and provide an inhibitory drive during hypercapnic conditions in both males and females at P7-8 and P14-15.
Usage: Anti-DBH-SAP (420 ng/μL – 1 μL for P0-1; 1.5 μL for P7-8; 2.0 μL for P13-14) was injected into the 4th ventricle of neonatal Wistar rats of both sexes. Control rats were injected with vehicle (PBS, 0.01 M, pH 7.4) or unconjugated saporin (Cat. #PR-01), with respective volumes for each age, as described for the Anti-DBH-SAP group. All injections were performed using a microinjector pump over a period of 5 min to allow drug diffusion.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Potter H, Alenciks E, Frazier K, Porter A, Fraley GS (2018) Immunolesion of melanopsin neurons causes gonadal regression in Pekin drakes (Anas platyrhynchos domesticus). Gen Comp Endocrinol 256:16-22. doi: 10.1016/j.ygcen.2017.08.006Objective: Examine effects of loss of melanopsin in drakes.
Summary: Loss of melanopsin in PMM elicits decrease in GnRH mRNA expression, gonadal regression, and sex behaviors in drakes.
Usage: To specifically lesion melanopsin-receptive neurons, 3 μl of an anti-melanopsin-saporin conjugate (MSAP, 100 ng/ul) was injected into the lateral ventricle (n = 10). Control drakes were injected with 3 μl of equimolar unconjugated anti-melanopsin and saporin (SAP, n = 10).
Related Products: Melanopsin-SAP (Cat. #IT-44), Saporin (Cat. #PR-01)
Raphe pallidus is not important to central chemoreception in a rat model of Parkinson’s disease.
Oliveira LM, Moreira TS, Takakura AC (2018) Raphe pallidus is not important to central chemoreception in a rat model of Parkinson’s disease. Neuroscience 369:350-362. doi: 10.1016/j.neuroscience.2017.11.038
Objective: To investigate if serotonin-expressing neurons in the Raphe pallidus/parapyramidal region (RPa/PPy) are also involved in the modulation of breathing during central chemoreception activation in a PD animal model.
Related Products: Anti-SERT-SAP (Cat. #IT-23), Saporin (Cat. #PR-01)
Site-specific regulation of P2X7 receptor function in microglia gates morphine analgesic tolerance.
Leduc-Pessah H, Weilinger N, Fan C, Burma N, Thompson R, Trang T (2017) Site-specific regulation of P2X7 receptor function in microglia gates morphine analgesic tolerance. J Neurosci 37:10154-10172.. doi: 10.1523/JNEUROSCI.0852-17.2017
Summary: By selectively ablating microglia in the spinal cord using a Mac-1-SAP the authors demonstrate a causal role for microglia in the development, but not maintenance, of morphine tolerance in male rats.
Usage: Mac-1-SAP or unconjugated Saporin control (15 μg) was administered by intrathecal injection.
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)
Spinal microglia are required for long-term maintenance of neuropathic pain
Echeverry S, Shi XQ, Yang M, Huang H, Wu Y, Lorenzo L-E, Perez-Sanchez J, Bonin RP, De Koninck Y, Zhang J (2017) Spinal microglia are required for long-term maintenance of neuropathic pain. Pain 158:1792-1801.. doi: 10.1097/j.pain.0000000000000982
Summary: Selective depletion of spinal microglia in male rats with the targeted immunotoxin Mac-1-SAP and blockade of brain derived neurotrophic factor–TrkB signalling with intrathecal TrkB Fc chimera, but not cytokine inhibition, almost completely reversed pain hypersensitivity. To selectively deplete microglia in the spinal cord, Mac-1-SAP was injected intrathecally. In each group, rats received either an intrathecal injection of 12 mg/7 mL of Mac-1-SAP (n = 6-8) or equal volume of 0.9% saline (n 5 6) or the inactive unconjugated toxin, Saporin (n = 6).)
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)
Nichols NL, Craig TA, Tanner MA (2018) Phrenic long-term facilitation following intrapleural CTB-SAP-induced respiratory motor neuron death. Respir Physiol Neurobiol 256:43-49. doi: 10.1016/j.resp.2017.08.003Objective: To study the impact of respiratory motor neuron death.
Summary: Intrapleural CTB-SAP mimics aspects of ALS. Seven days of CTB-SAP enhances respiratory plasticity.
Usage: Bilateral intrapleural injections of: 1) CTB-SAP (25 μg), or 2) unconjugated CTB and SAP (control).
Related Products: CTB-SAP (Cat. #IT-14), Saporin (Cat. #PR-01)
Blocking microglial pannexin-1 channels alleviates morphine withdrawal in rodents
Burma NE, Bonin RP, Leduc-Pessah H, Baimel C, Cairncross ZF, Mousseau M, Shankara JV, Stemkowski PL, Baimoukhametova D, Bains JS, Antle MC, Zamponi GW, Cahill CM, Borgland SL, De Koninck Y, Trang T (2017) Blocking microglial pannexin-1 channels alleviates morphine withdrawal in rodents. Nat Med 23:355-360.. doi: 10.1038/nm.4281
Summary: The authors investigated the mechanisms underlying opiate withdrawal in rat. Depletion of spinal lumbar microglia by intrathecal injections of Mac-1–SAP (Cat. #IT-33; 20 mcg) decreased withdrawal behaviors and attenuated the severity of withdrawal without affecting morphine antinociception. Unconjugated Saporin (Cat. #PR-01; 20 mcg) was used as control and had no effect on spinal CD11b immunoreactivity or naloxone-induced morphine withdrawal.
Related Products: Mac-1-SAP rat (Cat. #IT-33), Saporin (Cat. #PR-01)
Limiting glucocorticoid secretion increases the anorexigenic property of Exendin-4.
Lee S, Diener K, Kaufman S, Krieger J, Pettersen K, Jejelava N, Arnold M, Watts A, Langhans W (2016) Limiting glucocorticoid secretion increases the anorexigenic property of Exendin-4. Mol Metab 5:552-565. doi: 10.1016/j.molmet.2016.04.008
Summary: Glucagon-like peptide-1 (GLP-1) analogs lower blood surgar levels and cause a loss of appetite. Exendin-4 (Ex-4) is a GLP-1 receptor agonist, and also increases glucocorticoid secretion. Several tests were conducted to determine if the released glucocorticoids interact with Ex-4’s anorexigneic effect. One method involved ablating hindbrain catecholaminergic neurons by stereotaxically injecting 42 ng of Anti-DBH-SAP (Cat. #IT-03) bilaterally into the paraventricular nucleus of the hypothalamus in rats. Animals were injected with equimolar concentrations of unconjugated Saporin (Cat. #PR-01) as a control. Anti-DBH-SAP lesions reduced the efficacy of Ex-4 to increase corticosterone secretion but increased the anorexigenic effect, indicating that Ex-4-dependent corticosterone secretion opposes Ex-4’s actions. Anti-DBH-SAP lesions increased Ex-4’s ability to reduce food intake and body weight.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Sedlik C, Heitzmann A, Viel S, Ait Sarkouh R, Batisse C, Schmidt F, De La Rochere P, Amzallag N, Osinaga E, Oppezzo P, Pritsch O, Sastre-Garau X, Hubert P, Amigorena S, Piaggio E (2016) Effective antitumor therapy based on a novel antibody-drug conjugate targeting the Tn carbohydrate antigen. Oncoimmunology 5:e1171434. doi: 10.1080/2162402X.2016.1171434
Summary: Scientists wanted to study the potential of Chi-Tn, a monoclonal antibody against a glycol-peptidic tumor-associated antigen, as an anticancer antibody-drug conjugate. They demonstrated that Chi-Tn specifically targeted tumor cells in vivo, using flow cytometry and deconvolution microscopy to show that Chi-Tn is rapidly internalized. Chi-Tn-SAP (ATS Custom Services) effectively killed Tn-positive cells, but had no effect on Tn-negative cells. Saporin (Cat. #PR-01) was used as control. The cytotoxicity of the Chi-Tn-SAP correlated with the level of tumoral Tn expression.
Related Products: Saporin (Cat. #PR-01), Custom Conjugates
Functional characterization of a mouse model for central post-stroke pain.
Gritsch S, Bali K, Kuner R, Vardeh D (2016) Functional characterization of a mouse model for central post-stroke pain. Mol Pain 12:1744806916629049. doi: 10.1177/1744806916629049
Summary: While clinical evidence has pointed toward central pain pathway dysfunction in central post-stroke pain (CPSP), the underlying mechanisms have not been defined. In this work the authors created a mouse model of CPSP through lesions of the thalamic ventral posterolateral nucleus. In order to examine the role of neurokinin-1 receptor-expressing (NK1R) neurons in lamina I/III of the spinal cord in the development and maintenance of CPSP the authors administered 1 μmol intrathecal injections of SSP-SAP (Cat. #IT-11). Saporin (Cat. #PR-01) was used as a control. While the NK1R+ neurons in the spinal cord were not involved in establishing CPSP, the data indicate that sensory changes in the mice are comparable to those observed in human patients with CPSP.
Related Products: SSP-SAP (Cat. #IT-11), Saporin (Cat. #PR-01)
Roles of isolectin B4-binding afferents in colorectal mechanical nociception.
La J, Feng B, Kaji K, Schwartz E, Gebhart G (2016) Roles of isolectin B4-binding afferents in colorectal mechanical nociception. Pain 157:348-354. doi: 10.1097/j.pain.0000000000000380
Summary: Primary afferent neurons are often classified as peptidergic or non-peptidergic. One characteristic of the non-peptidergic neurons is that they bind isolectin-B4. In the spinal cord these neurons terminate mainly in inner lamina II. Non-peptidergic neurons in the spinal cord have been found to be involved in various aspects of pain response. In this work the authors examined the role of non-peptidergic neurons in the viscerosensory system. Rats received 1.5 μg of intrathecal recombinant IB4-SAP (Cat. #IT-10) between the L5 and L6 vertebrae. Saporin (Cat. #PR-01) was used as a control. While IHC demonstrated that a majority of viscerosensory L6 colon DRG neurons are IB4+, they do not play a significant role in colorectal mechano-nociception.
Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)
Harasawa I, Johansen J, Fields H, Porreca F, Meng I (2016) Alterations in the rostral ventromedial medulla after the selective ablation of μ-opioid receptor expressing neurons. Pain 157:166-173. doi: 10.1097/j.pain.0000000000000344
Summary: The rostral ventromedial medulla (RVM) has both excitatory and inhibitory control over nociceptive neurons in the medullary dorsal horn and spinal cord. Previous work has demonstrated that elimination of mu-opioid receptor-expressing neurons in the RVM reduces stress and injury-induced behavioral hypersensitivity, but the effect of losing these cells on the descending inhibitory system has not been examined. The authors administered 1.2 pmol of Dermorphin-SAP (Cat. #IT-12) to each side of the RVM of rats. Saporin (Cat. #PR-01) was used as a control. Characterization of RVM neurons in lesioned animals showed a reduction in on- and off-cells, but no change in the number of neutral cells. These data indicate that mu-opioid receptor-expressing cells in the RVM are not needed for analgesia produced by activation of RVM neurons.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Saporin (Cat. #PR-01)
Ostock CY, Conti MM, Larose T, Meadows S, Bishop C (2015) Cognitive and motor deficits in a rodent model of Parkinson’s disease displaying concurrent dopamine and acetylcholine loss. Neuroscience 2015 Abstracts 676.26/D33. Society for Neuroscience, Chicago IL.
Summary: Dopamine (DA) loss in Parkinson’s disease (PD) is frequently accompanied by degeneration of acetylcholine neurons within the basal forebrain (BF) and the pedunculopontine nucleus (PPN). Recently, Ach neurons in these nuclei have been implicated in both the motor and non-motor symptoms of PD. However, few rodent models of PD actually account for Ach loss in both the BF and PPN. Here, we evaluated the effects of concurrent BF and PPN Ach loss alone and in combination with striatal DA loss on motor and cognitive performance in a rat model of PD. Sprague-Dawley rats (N = 44) received bilateral: striatal 6-OHDA lesions to deplete DA (DA-lesioned; n = 14), BF (192 IgG-Saporin) and PPN (anti-ChAT Saporin) saporin lesions to deplete Ach (Ach-lesioned; n = 10), combined 6-OHDA + saporin lesions (dual-lesioned; n = 6) , or sham lesions (n = 14). Following recovery from surgery, rats underwent a battery of motor and cognitive behavioral tests. Results indicated that Ach-lesioned and dual-lesioned rats displayed spatial memory deficits on the Morris Water Maze and Spontaneous Alternation tests. DA and Ach lesions alone impaired stepping for the forepaw adjusting steps and vibrissae-elicited paw placement tests and this deficit was exacerbated in dual-lesioned rats. However, only rats with Ach or dual lesions showed motor deficits on the rotarod tests. Collectively, these findings demonstrate that Ach loss may exacerbate cognitive and motor symptoms in PD and highlight the importance of including Ach loss in preclinical models of PD.
Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-ChAT-SAP (Cat. #IT-42), Saporin (Cat. #PR-01)
Alenciks E, Frazier K, Porter A, Fraley G (2015) Immunolesions of melanopsin receptive neurons attenuates the hormonal reproductive axis in the adult but has no effect on growth in immature Peking ducks. Neuroscience 2015 Abstracts 613.05/R20. Society for Neuroscience, Chicago IL.
Summary: Several light sensitive receptors have been described in the avian brain that are thought to regulate the reproductive axis independently from the eyes and pineal gland. Recently, our lab has described the presence of 3 photoneuroendocrine systems in the Pekin duck: rhodopsin, opsin 5, & melanopsin. We set out to test the hypothesis that melanopsin receptive neurons are necessary to maintain seasonal reproductive status along with growth and development in the Pekin drake. To accomplish these goals we first investigated 50-week-old Pekin drakes that were housed in the aviary at Hope College under long day length (18 hrs lights on) conditions in floor pens. To specifically lesion melanopsin-receptive neurons, 3 μl of an anti-melanopsin-saporin conjugate (MSAP, 100 ng/ul) was injected into the lateral ventricle (n = 10). Control drakes were injected with 3 ul of equimolar unconjugated anti-melanopsin and saporin (SAP, n = 10). The drakes were returned to the aviary after complete recovery. Reproductive behaviors were analyzed weekly in a test pen with adult hens. After 4 weeks, birds were euthanized and body weights were measured, and brains, pituitaries, and testes collected and stored for analyses. To test melanopsin’s effect on immature ducks the same surgery was performed on a group of 10 day old ducks (n= 10). Ducks were weighed weekly starting at 3 days of age. After a final weight was obtained at 50 days of age, ducks were euthanized and a blood sample was collected and sent out for an avian panel. Mature MSAP-treated drakes had significantly (p< 0.001) reduced relative teste weights compared to SAP controls. qRT-PCR analyses (n= 3 per treatment) of anterior pituitary showed a significant reduction (p< 0.001) in both LH-beta and FSH mRNA’s. Immunoctyochemical analyses (n= 3 per treatment) showed a significant reduction in melanopsin and GnRH-immunoreactivities. Immature drake BW did not differ significantly between MSAP and SAP animals at any of the measured days. The data appeared to drift toward significance near the end of the sampling period (p = 0.297). Blood panel results revealed no significant differences between MSAP and SAP animals in any CBC component. Serum glutamic-oxaloacetic transaminase (SGOT) (p= 0.022) and creatine phosphokinase (CPK) values were significantly elevated (p = 0.006) in MSAP animals compared to controls. Although melanopsin neurons in the PMM appear to have an important role in adult drakes, their importance in the growth of immature ducks is still unclear. However, these data underscore the importance of the photoneuroendocrine system in maintaining the reproductive axis along with growth and development in seasonally breeding birds.
Related Products: Melanopsin-SAP (Cat. #IT-44), Saporin (Cat. #PR-01)
Porter LM, Alenciks E, Frazier K, Porter A, Fraley GS (2015) Lack of effects on growth and body weight gain after elimination of the leptin receptor from the brain of immature Pekin drakes. Neuroscience 2015 Abstracts 613.04/R19. Society for Neuroscience, Chicago IL.
Summary: The presence of the hormone leptin (LEP) is a controversial topic in the field of avian physiology. While LEP is well understood in mammals, the hormone has not been definitively verified in avian species. Although the hormone remains elusive, the leptin receptor (LEPR) has been identified and sequenced in multiple avian species. Its role, however, remains unclear. To attempt to deduce the role of the leptin system in birds, we focused on altering the leptin receptor expression in the brain of immature Pekin ducks. We hypothesized that eliminating the LEPR-expressing neurons of the hypothalamus would elicit an increase in body weight, as is the case for mammals. To test this hypothesis, we injected stereotaxically 3 ul of a solution containing a monoclonal antibody (anti-LEPR) conjugated to saporin (LSAP, 100 ng/ul) was injected into the lateral ventricle of 10 day old Pekin ducks (LSAP, N = 10). Control group animals (SAP) were injected with unconjugated antibody and saporin at equimolar concentrations to the LSAP. Ducks were weighed weekly starting at 3 days of age. After a final weight was obtained at 50 days of age, ducks were euthanized and a blood sample was collected and sent out for an avian panel to assay serum glucose and free fatty acids. We found that the elimination of LEPR had no significant effect on the body weights of the ducks (p>0.05). In addition, The CBC panel did not reveal any significant differences in the overall health of the ducks in each treatment group. Our data indicates LEPR may not play a significant role in the regulation of body weight or growth in juvenile ducks.
Related Products: Custom Conjugates, Saporin (Cat. #PR-01)
Devoto P, Flore G, Saba P, Frau R, Gessa G (2015) Selective inhibition of dopamine-beta-hydroxylase enhances dopamine release from noradrenergic terminals in the medial prefrontal cortex. Brain Behav 5:e00393. doi: 10.1002/brb3.393
Summary: Dopamine-beta-hydroxylase (DBH) is a neuronal enzyme that is a potential target for the treatment of cocaine abuse, alcohol dependence, and eating disorders. Here the authors administered 5 μg of icv Anti-DBH-SAP (Cat. #IT-03) to rats, and assessed the effect of the dopaminergic lesion on levels of extracellular dopamine. Mouse IgG-SAP (Cat. #IT-18) and saporin (Cat. #PR-01) were used as controls. Extracellular levels of dopamine were significantly increased in both lesioned animals and those treated with the DBH inhibitor nepicastat. Clonadine could reverse the nepicastat effect, but not the effect of Anti-DBH-SAP treatement. The data demonstrate a mechanism for the synergistic effect of cocaine on nepicastat-induced dopamine release.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18), Saporin (Cat. #PR-01)
Kras J, Weisshaar C, Pall P, Winkelstein B (2015) Pain from intra-articular NGF or joint injury in the rat requires contributions from peptidergic joint afferents. Neurosci Lett 604:193-198. doi: 10.1016/j.neulet.2015.07.043
Summary: Both peptidergic and non-peptidergic neurons innervate the facet joint, which is the source of pain in a majority of neck trauma. In this work the authors examined these subpopulations of neurons to determine the contribution of each in facet joint pain. 100 ng of SSP-SAP (Cat. #IT-11) was injected into bilateral C6/C7 facet joints of rats. Alternatively, rats received 5 μg of rIB4-SAP (Cat. #IT-10) via the same method. Saporin (Cat. #PR-01) was used as control. SSP-SAP, but not rIB4-SAP was able to prevent NGF-induced mechanical and thermal hypersensitivity. SSP-SAP administration also prevented behavioral hypersensitivity and NGF upregulation in the dorsal root ganglion after facet joint distraction. The data indicate that interference with peptidergic signaling within the facet joint may be a treatment for pain originating in that location.
Related Products: SSP-SAP (Cat. #IT-11), IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)
Striatal patch compartment lesions reduce stereotypy following repeated cocaine administration.
Murray R, Logan M, Horner K (2015) Striatal patch compartment lesions reduce stereotypy following repeated cocaine administration. Brain Res 1618:286-298. doi: 10.1016/j.brainres.2015.06.012
Summary: Stereotypy is defined as abnormally repetitive motor movements accompanied by an inability to initiate normal adaptive responses. Psychostimulants such as cocaine will often produce these movements. It is thought that stereotypy is related to activation of the patch compartment of the striatum. In order to better understand the function of the patch compartment in stereotypy due to repeated exposure to cocaine, the authors administered bilateral injections of Dermorphin-SAP (Cat. #IT-12) into the rostral striatum. Saporin (Cat. #PR-01) was used as a control.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Saporin (Cat. #PR-01)
Orexin-A enhances feeding in male rats by activating hindbrain catecholamine neurons.
Li A, Wang Q, Davis H, Wang R, Ritter S (2015) Orexin-A enhances feeding in male rats by activating hindbrain catecholamine neurons. Am J Physiol Regul Integr Comp Physiol 309:R358-367. doi: 10.1152/ajpregu.00065.2015
Summary: Although administration of orexin, norepinephrine, and epinephrine all induce significantly increased food intake, the potential interaction between the networks affected by these molecules has not been studied. In this work, the authors investigate the hypothesis that orexin neurons may stimulate feeding through the activation of catecholamine neurons. Rats received 82-ng injections of Anti-DBH-SAP (Cat. #IT-03) into the hypothalamus in order to lesion hypothalamically-projecting catecholamine neurons. Saporin (Cat. #PR-01) was used as a control. While the normal response to orexin A is increased food intake, lesioned animals did not display this response, indicating that catecholamine neurons are necessary for orexin modulation of food intake.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Different immune cells mediate mechanical pain hypersensitivity in male and female mice.
Sorge R, Mapplebeck J, Rosen S, Beggs S, Taves S, Alexander J, Martin L, Austin J, Sotocinal S, Chen D, Yang M, Shi X, Huang H, Pillon N, Bilan P, Tu Y, Klip A, Ji R, Zhang J, Salter M, Mogil J (2015) Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nat Neurosci 18:1081-1083. doi: 10.1038/nn.4053
Summary: A large and rapidly increasing body of evidence indicates that microglia-to-neuron signaling is essential for chronic pain hypersensitivity. Using multiple approaches, the authors found that microglia are not required for mechanical pain hypersensitivity in female mice; female mice achieved similar levels of pain hypersensitivity using adaptive immune cells, likely T lymphocytes. This sexual dimorphism suggests that male mice cannot be used as proxies for females in pain research. Mac-1-SAP mouse/human toxin (Cat. #IT-06, 15 μg in 8.8 μl) and Saporin control (Cat. #PR-01, 8.8 μg in 8.8 μl) were administered via i.t. injection. The topic of immune system involvement in chronic pain pathophysiology is one of the most active in the pain field; that this sex difference has not been observed until now is very surprising indeed. An important implication of the current findings is that distinct strategies targeting neuroimmune signaling might be required for the treatment of chronic pain in men versus women.
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)
Bostad M, Olsen C, Peng Q, Berg K, Høgset A, Selbo P (2015) Light-controlled endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin by photochemical internalization - A minimally invasive cancer stem cell-targeting strategy. J Control Release 206:37-48. doi: 10.1016/j.jconrel.2015.03.008
Summary: Previously the authors demonstrated the use of photochemical internalization of a custom conjugate consisting of a CD133 antibody coupled to saporin (ATS Custom conjugation). Several cancer cell lines were plated, and incubated in the presence of a photosensitizer with either CD133-SAP at 8.6 pM or Saporin (Cat. #PR-01) at 24 pM. The different concentrations equalized the number of saporin molecules in each sample. A light source was used to initiate the internalization of the molecules. The results indicate that this is a viable strategy for the targeted treatment of cancer stem cells.
Related Products: Anti-CD133-SAP (Cat. #IT-82), Saporin (Cat. #PR-01), Custom Conjugates
Hindbrain catecholamine neurons activate orexin neurons during systemic glucoprivation in male rats.
Li A, Wang Q, Elsarelli M, Brown R, Ritter S (2015) Hindbrain catecholamine neurons activate orexin neurons during systemic glucoprivation in male rats. Endocrinology 156:2807-2820. doi: 10.1210/en.2015-1138
Summary: Norepinephrine and epinephrine-secreting catecholamine neurons are strong stimulators of food intake. The authors investigated the interaction between these catecholamine neurons and orexin neurons in the perifornical lateral hypothalamus (PeFLH), which are known to be involved with the stimulation of food intake, increased arousal, and behavioral activation. Rats received 82-ng injections of Anti-DBH-SAP (Cat. #IT-03) into the PeFLH terminal field in order to lesion catecholamine neurons. Saporin (Cat. #PR-01) was used as a control. Assessment of food intake in response to 2-deoxy-D-glucose, as well as selective catecholamine activation, indicated that orexin neuron activation may be involved in glucoprivic appetite responses.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Endogenous opioid activity in the anterior cingulate cortex is required for relief of pain.
Navratilova E, Xie J, Meske D, Qu C, Morimura K, Okun A, Arakawa N, Ossipov M, Fields H, Porreca F (2015) Endogenous opioid activity in the anterior cingulate cortex is required for relief of pain. J Neurosci 35:7264-7271. doi: 10.1523/JNEUROSCI.3862-14.2015
Summary: There are a number of neuronal circuits involved in the processing of pain, including those that control somatosensory, affective, and cognitive aspects of pain perception. Opioid signaling in the anterior cingulate cortex (ACC) plays a part in pain modulation - this area has also been implicated in the encoding of pain aversiveness. In order to examine the neuronal mechanisms of pain relief and the following reward, the authors of this paper administered 48 ng of Dermorphin-SAP (Cat. #IT-12) into the rostral ACC of rats. Saporin (Cat. #PR-01) was used as a control. The results illuminate the opioid pathway during pain treatment, and the dependence of nucleus accumbens dopaminergic transmission on upstream ACC opioid circuits during pain processing.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Saporin (Cat. #PR-01)
Nichols N, Vinit S, Bauernschmidt L, Mitchell G (2015) Respiratory function after selective respiratory motor neuron death from intrapleural CTB-saporin injections. Exp Neurol 267:18-29. doi: 10.1016/j.expneurol.2014.11.011
Summary: Amyotrophic lateral sclerosis (ALS) ultimately causes death from ventilator failure. Genetic models of ALS suffer from high variability of the rate, timing, and extent of respiratory motor neuron death. The authors created a novel model of induced respiratory motor neuron death using CTB-SAP (Cat. #IT-14). Rats received 25 μg or 50 μg intrapleural injections of CTB-SAP; Saporin (Cat. #PR-01) was used as a control. After 7 days, motor neuron survival approximated what is seen in end-stage ALS rats, while there was minimal cell death in other brainstem or spinal cord regions. CTB-SAP also caused microglial activation, decreased breathing during chemoreceptor stimulation, and diminished phrenic motor output in anesthetized rats – all hallmarks of ALS.
Related Products: CTB-SAP (Cat. #IT-14), Saporin (Cat. #PR-01)
Ono K, Ye Y, Viet C, Dang D, Schmidt B (2015) TRPV1 expression level in isolectin B₄-positive neurons contributes to mouse strain difference in cutaneous thermal nociceptive sensitivity. J Neurophysiol 113:3345-3355. doi: 10.1152/jn.00973.2014
Summary: In order to determine whether IB4-positive trigeminal sensory neurons affect pain sensitivity, the authors administered 2 μg of rIB4-SAP (Cat. #IT-10) to the right infraorbital foramen. Saporin (Cat. #PR-01) was used as a control.
Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)
Wu Y, Song S, Liu H, Xing D, Wang X, Fei Y, Li G, Zhang C, Li Y, Zhang L (2015) Role of adrenomedullin in the cerebrospinal fluid-contacting nucleus in the modulation of immobilization stress. Neuropeptides 51:43-54. doi: 10.1016/j.npep.2015.03.007
Summary: The CSF-contacting nucleus (CSF-CN) is a brain structure containing neurons that can bidirectionally transmit signals between the brain parenchyma and the CSF. In order to better understand what regulatory peptides modulate this organ, the authors eliminated the CSF-CN of rats with a 500-ng icv injection of CTB-SAP (Cat. #IT-14). Saporin (Cat. #PR-01) was used as a control. The elimination of the CSF-CN worsened the response to chronic immobilization stress; with other data this information suggests that the CSF-CN uses adrenomedullin as a stress-related peptide.
Related Products: CTB-SAP (Cat. #IT-14), Saporin (Cat. #PR-01)
Dashniani M, Burjanadze M, Naneishvili T, Chkhikvishvili N, Beselia G, Kruashvili L, Pochkhidze N, Chighladze M (2015) Exploratory behavior and recognition memory in medial septal electrolytic, neuro- and immunotoxic lesioned rats. Physiol Res 64:755-767. doi: 10.33549/physiolres.932809
Summary: To investigate recognition memory that incorporates a spatial or temporal component, the authors lesioned the medial septum of rats using several techniques. For specific lesioning of cholinergic neurons rats received bilateral injections of 192-IgG-SAP (Cat. #IT-01, 500 ng total) into the medial septum. Saporin (Cat. #PR-01) was used as a control. While electrolytic lesions produced disruptions of spatial recognition memory, immunotoxin lesions did not, indicating that the cholinergic neurons of the septohippocampal pathway are not essential to processing this type of learning.
Related Products: 192-IgG-SAP (Cat. #IT-01), Saporin (Cat. #PR-01)
Burjanadze M, Mataradze S, Rusadze K, Chkhikvishvili N, Dashniani M (2015) Selective lesion of GABA-ergic neurons in the medial septum by GAT1-saporin impairs spatial learning in a water-maze. Georgian Med News 240:59-64.
Summary: The authors investigated the role of GABAergic neurons in the medial septum on spatial learning using a Morris water maze test. Rats received bilateral injections totaling 162 ng of GAT-1-SAP (Cat. #IT-32) into the medial septum. Saporin (Cat. #PR-01) was used as a control. The lesioned animals displayed significant deficits during the water maze task, indicating that GABAergic neurons in the medial septum are intrinsic to organization of spatial map-driven behavior.
Related Products: GAT1-SAP (Cat. #IT-32), Saporin (Cat. #PR-01)
Dashniani M, Kruashvili L, Rusadze K, Matatradze S, Beselia G (2015) Effects of immunotoxic and electrolytic lesions of medial septal area on spatial short-term memory in rats. Georgian Med News 239:98-103.
Summary: In this work the authors investigated how essential septohippocampal projections are in a spatial working memory model. Rats received bilateral injections of 192-IgG-SAP (Cat. #IT-01, 600 ng total) or GAT-1-SAP (Cat. #IT-32, 195 ng total) into the medial septum. Saporin (Cat. #PR-01) was used as a control.
Related Products: 192-IgG-SAP (Cat. #IT-01), GAT1-SAP (Cat. #IT-32), Saporin (Cat. #PR-01)
Liu H, Yan W, Lu X, Zhang X, Wei J, Wang X, Wang T, Wu T, Cao J, Shao C, Zhou F, Zhang H, Zhang P, Zang T, Lu X, Cao J, Ding H, Zhang L (2014) Role of the cerebrospinal fluid-contacting nucleus in the descending inhibition of spinal pain transmission. Exp Neurol 261:475-485. doi: 10.1016/j.expneurol.2014.07.018
Summary: The first synapse in the pain pathway is in the spinal dorsal horn, and several sites are involved in the descending control of pain. Previous studies have suggested that cerebrospinal fluid-contacting neurons may facilitate signal transmission and substance transport between the brain parenchyma and the CSF, including processes that modulate pain transmission. The authors administered CTB-SAP (Cat. #IT-14) into the right lateral ventricle of rats. Saporin (Cat. #PR-01) was used as a control. The results indicate that the 5-HT pathway contacting the CSF is an important piece in the descending inhibitory system controlling spinal transmission of pain.
Related Products: CTB-SAP (Cat. #IT-14), Saporin (Cat. #PR-01)
Flak J, Myers B, Solomon M, McKlveen J, Krause E, Herman J (2014) Role of paraventricular nucleus-projecting norepinephrine/epinephrine neurons in acute and chronic stress. Eur J Neurosci 39:1903-1911. doi: 10.1111/ejn.12587
Summary: Chronic stress can cause dysregulation of the paraventricular nucleus (PVN) of the hypothalamus, resulting in structural and function changes in the neurons involved. There are data indicating that post-stress enhancement of norepinephrine is involved in the processing of chronic stress. In this work the authors investigated the hypothesis that PVN-projecting norepinephrine/epinephrine (NE/E) neurons are necessary for chronic stress-induced drive of the hypothalamic-pituitary-adrenocortical (HPA) axis. Rats received bilateral 8.82 ng injections of anti-DBH-SAP (Cat. #IT-03) into the PVN. Saporin (Cat. #PR-01) was used as a control. Lesioned animals displayed attenuated peak ACTH, indicating that NE/E neurons are required for ACTH release in the HPA axis during chronic stress.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Li AJ, Wang Q, Dinh TT, Powers BR, Ritter S (2014) Stimulation of feeding by three different glucose-sensing mechanisms requires hindbrain catecholamine neurons. Am J Physiol Regul Integr Comp Physiol 306(4):R257-R264. doi: 10.1152/ajpregu.00451.2013
Summary: The glucoregulatory system of the brain requires catecholamine neurons in the hindbrain. he sensory mechanisms and connected circuitry controlling the response to glucose deficit are not well understood. In order to investigate different drugs that stimulate food intake but interfere with cellular glucose metabolism and transport the authors administered 82 ng of anti-DBH-SAP (Cat. #IT-03) into the paraventricular nucleus as bilateral injections. Saporin (Cat. #PR-01) was used as a control. Lesioned animals did not increase food intake in response to any of the drugs, indicating that stimulation of food intake is activated through a catecholamine-dependent pathway.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Ye Y, Bae S, Viet CT, Troob S, Bernabe D, Schmidt BL (2014) IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma. Behav Brain Funct 10(1):5. doi: 10.1186/1744-9081-10-5
Objective: To evaluate subtypes of sensory neurons involved in cancer pain and proliferation.
Summary: IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics.
Usage: IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics.
Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)
Featured Article: Role of spinal microglia in the development of morphine-induced hyperalgesia
Ferrini F, De Koninck Y (2013) Featured Article: Role of spinal microglia in the development of morphine-induced hyperalgesia. Targeting Trends 14(4)
Related Products: Mac-1-SAP rat (Cat. #IT-33), Saporin (Cat. #PR-01)
Read the featured article in Targeting Trends.
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Li AJ, Wang Q, Dinh TT, Wiater MF, Eskelsen AK, Ritter S (2013) Hindbrain catecholamine neurons control rapid switching of metabolic substrate use during glucoprivation in male rats. Endocrinology 154(12):4570-4579. doi: 10.1210/en.2013-1589
Summary: Previous work has shown that corticosterone secretion in response to glucoprivation is at least in part controlled by hindbrain catecholamine neurons in the paraventricular nucleus of the hypothalamus (PVH). In this work the authors investigate the metabolic consequences of lesioning these neurons. Rats received bilateral 82-ng infusions of Anti-DBH-SAP (Cat. #IT-03) into the PVH. Saporin (Cat. #PR-01) was used as a control. Although lesioned animals had the same energy expenditure and locomotor activity as controls, they also had a higher respiratory exchange ratio, indicating a reduced ability to switch from carbohydrate to fat metabolism in response to glucoprivation.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
da Silva EF, Freiria-Oliveira AH, Custodio CH, Ghedini PC, Bataus LA, Colombari E, de Castro CH, Colugnati DB, Rosa DA, Cravo SL, Pedrino GR (2013) A1 noradrenergic neurons lesions reduce natriuresis and hypertensive responses to hypernatremia in rats. PLoS One 8(9):e73187. doi: 10.1371/journal.pone.0073187
Summary: Using bilateral 63-ng injections of Anti-DBH-SAP (Cat. #IT-03) into two levels of the caudal ventrolateral medulla, the authors assessed several pressor responses to infusion of hypertonic saline. Saporin (Cat. #PR-01) was used as a control. The results suggest that medullary noradrenergic A1 neurons are involved in the regulation of some responses to acute changes in body fluid composition.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Implication of cerebral dopamine-beta hydroxylase for cardiovascular and mood regulation in rats.
Chang ST, Liu YP, Huang CL, Wang PY, Tung CS (2013) Implication of cerebral dopamine-beta hydroxylase for cardiovascular and mood regulation in rats. Chin J Physiol 56(4):209-218. doi: 10.4077/CJP.2013.BAB103
Summary: The ascending fibers affected by norepinephrine are involved in a variety of processes, including emotion, anxiety, and regulation of central autonomic outflows such as cardiovascular regulation and energy balance. The authors examined whether the loss of norephinephrine would cause autonomic failure in cardiovascular regulation. Rats received a single intraventricular injection of anti-DBH-SAP (Cat. #IT-03). Saporin (Cat. #PR-01) was used as a control. The results demonstrate that norepinephrine deficits in the brain influence reduction of excitatory responses to orthostatic stress.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Shia WW, Bailey RC (2013) Single domain antibodies for the detection of ricin using silicon photonic microring resonator arrays. Anal Chem 85(2):805-810. doi: 10.1021/ac3030416
Summary: A major hurdle to clear in the fight against bioterrorism is the ability to identify various biowarfare agents. One of the more difficult substances to identify is ricin. This work describes the use of single domain antibodies to identify ricin in a microring resonator array assay. Saporin (Cat. #PR-01) along with affinity purified chicken anti-saporin (Cat. #AB-17AP) were used as controls when constructing the assay. The results demonstrate the feasibility of using microring resonator arrays for the detection of biowarfare agents.
Related Products: Saporin Chicken Polyclonal, affinity-purified (Cat. #AB-17AP), Saporin (Cat. #PR-01)
Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl(-) homeostasis.
Ferrini F, Trang T, Mattioli TA, Laffray S, Del’Guidice T, Lorenzo LE, Castonguay A, Doyon N, Zhang W, Godin AG, Mohr D, Beggs S, Vandal K, Beaulieu JM, Cahill CM, Salter MW, De Koninck Y (2013) Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl(-) homeostasis. Nat Neurosci 16(2):183-192. doi: 10.1038/nn.3295
Summary: Although morphine is the drug of choice in dealing with chronic pain, it paradoxically can produce a hyperalgesic state. The authors examined the issue from several different angles. One method was to eliminate spinal microglia of rats through the intrathecal application of 16-32 μg of Mac-1-SAP (Cat. #IT-33). 20 μg of saporin (Cat. #PR-01) was used as a control. It was found that P2X4 receptors expressed by microglia were necessary for the development of morphine hyperalgesia, but not morphine tolerance.
Related Products: Mac-1-SAP rat (Cat. #IT-33), Saporin (Cat. #PR-01)
Cholinergic denervation attenuates phencyclidine-induced c-fos responses in rat cortical neurons.
Savage S, Mattsson A, Olson L (2012) Cholinergic denervation attenuates phencyclidine-induced c-fos responses in rat cortical neurons. Neuroscience 216:38-45. doi: 10.1016/j.neuroscience.2012.04.064
Summary: Phenylcyclidine (PCP) has been used to model aspects of schizophrenia in animals. 81 ng of 192-IgG-SAP (Cat. #IT-01) was injected into the nucleus basalis magnocellularis of rats to assess the effects of low dose PCP in a cholinergically-deprived system. Saporin (Cat. #PR-01) was used as a control. Results demonstrate basalocortical cholinergic neurons are necessary for PCP to have full effect.
Related Products: 192-IgG-SAP (Cat. #IT-01), Saporin (Cat. #PR-01)
Sikandar S, Bannister K, Dickenson AH (2012) Brainstem facilitations and descending serotonergic controls contribute to visceral nociception but not pregabalin analgesia in rats. Neurosci Lett 519(1):31-36. doi: 10.1016/j.neulet.2012.05.009
Summary: Neurons in the rostral ventromedial medulla (RVM) are classified as ON, OFF, or NEUTRAL based on firing patterns in response to noxious somatic stimulation. ON cells express μ-opioid receptors, and are therefore a target for dermorphin-SAP (Cat. #IT-12). The authors injected the RVM of rats with 3 pmol of dermorphin-SAP; Saporin (Cat. #PR-01) was used as a control. Results show the μ-opioid receptor population is not needed for the function of analgesics through the serotonergic system.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Saporin (Cat. #PR-01)
A2 noradrenergic lesions prevent renal sympathoinhibition induced by hypernatremia in rats.
Pedrino GR, Freiria-Oliveira AH, Almeida Colombari DS, Rosa DA, Cravo SL (2012) A2 noradrenergic lesions prevent renal sympathoinhibition induced by hypernatremia in rats. PLoS One 7(5):e37587. doi: 10.1371/journal.pone.0037587
Summary: It is thought that renal sympathetic nerve activity is a key component of the response to acute or chronic elevated concentrations of saline in the blood stream. The authors investigated what neurons are involved in the central control of these responses. Rats received bilateral 6.3 ng injections of anti-DBH-SAP (Cat. #IT-03) into the nucleus of the solitary tract. An equimolar amount (1.3 ng) of saporin (Cat. #PR-01) was used as a control. Loss of the A2 noradrenergic neurons altered the renal sympathetic nerve activity response to elevated saline, suggesting that these neurons help regulate the extracellular fluid compartment.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Taylor AM, Osikowicz M, Ribeiro-da-Silva A (2012) Consequences of the ablation of nonpeptidergic afferents in an animal model of trigeminal neuropathic pain. Pain 153(6):1311-1319. doi: 10.1016/j.pain.2012.03.023
Summary: The authors used IB4-SAP (Cat. #IT-10; 3.2 μg injected into the mental nerve) to eliminate C-fibers in the lower lip of rats to see if this was enough to induce the sprouting of autonomic fibers. Saporin alone (Cat. #PR-01) was used as a control. Only parasympathetic fibers sprouted in these animals, but after nerve ligation surgery both sympathetic and parasympathetic fibers sprouted.
Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)
Analgesia targeting IB4-positive neurons in cancer-induced mechanical hypersensitivity.
Ye Y, Dang D, Viet CT, Dolan JC, Schmidt BL (2012) Analgesia targeting IB4-positive neurons in cancer-induced mechanical hypersensitivity. J Pain 13(6):524-531. doi: 10.1016/j.jpain.2012.01.006
Summary: DOR (δ opioid receptor) agonists produce minimal side effects and do not lead to tolerance, making them potential alternatives to the widely used μ opioid receptor agonists. Utilizing the fact that DOR's are expressed by IB4-positive neurons, the authors injected the subarachnoid space between the L4 and L5 vertebrae of rats with 2.4 μg of IB4-SAP (Cat. #IT-10). 3 μg of saporin (Cat. #PR-01) was used as a control. The results indicate that pharmacological agents targeting IB4-positive neurons may have use in cancer pain treatment.
Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)
Han N, Zu JY, Chai J (2012) Spinal bombesin-recognized neurones mediate more nonhistaminergic than histaminergic sensation of itch in mice. Clin Exp Dermatol 37(3):290-295. doi: 10.1111/j.1365-2230.2011.04314.x
Summary: The authors administered 400 ng of Bombesin-SAP (Cat. #IT-40) to the lumbar spinal subarachnoid space of rats and evaluated the distribution of Fos-positive cells in the dorsal horn after stimulation. Saporin (Cat. #PR-01) was used as a control. The results demonstrate that the neurons eliminated by Bombesin-SAP are critical to both acute and chronic itch pathways, although they have more effect on nonhistaminergic sensation.
Related Products: Bombesin-SAP (Cat. #IT-40), Saporin (Cat. #PR-01)
Selbo PK, Weyergang A, Eng MS, Bostad M, Maelandsmo GM, Hogset A, Berg K (2012) Strongly amphiphilic photosensitizers are not substrates of the cancer stem cell marker ABCG2 and provides specific and efficient light-triggered drug delivery of an EGFR-targeted cytotoxic drug. J Control Release 159(2):197-203. doi: 10.1016/j.jconrel.2012.02.003
Summary: Many anti-cancer drugs are substrates of the ATP-binding cassette transporter ABCG2. Unfortunately ABCG2 is also thought to play an important role in multi-drug resistance and the protection of cancer stem cells against chemotherapeutics and photodynamic therapy. This paper examined whether photosensitizers used in photochemical internalization (PCI) are substrates for ABCG2. Streptavidin-ZAP (Cat. #IT-27) was combined with biotinylated EGF and applied to cells in culture; saporin (Cat. #PR-01) was used as a control. The data show that PCI with the EGF-saporin toxin did not utilize ABCG2 to enter cells.
Related Products: Streptavidin-ZAP (Cat. #IT-27), Saporin (Cat. #PR-01)
Choi JI, Koehrn FJ, Sorkin LS (2012) Carrageenan induced phosphorylation of Akt is dependent on neurokinin-1 expressing neurons in the superficial dorsal horn. Mol Pain 8(1):4. doi: 10.1186/1744-8069-8-4
Summary: In this work the authors administered 100 ng SSP-SAP (Cat. #IT-11) into the intrathecal space of rats (saporin, Cat. #PR-01, was used as a control). Lesioned animals displayed decreased carrageenan-induced mechanical allodynia, and carrageenan-induced phosphorylation of Akt was blocked throughout the spinal cord gray matter. Anti-NK-1 (Cat. #AB-N33AP) was used for immunohistochemistry.
Related Products: SSP-SAP (Cat. #IT-11), Saporin (Cat. #PR-01), NK-1 Receptor Rabbit Polyclonal, affinity-purified (Cat. #AB-N33AP)
Staudt MD, Truitt WA, McKenna KE, de Oliveira CV, Lehman MN, Coolen LM (2012) A pivotal role of lumbar spinothalamic cells in the regulation of ejaculation via intraspinal connections. J Sex Med 9(9):2256-2265. doi: 10.1111/j.1743-6109.2011.02574.x
Summary: The authors examined the hypothesis that specific lumbar spinothalamic (LSt) cells control ejaculation through intraspinal connections. Rats received six bilateral injections of SSP-SAP (Cat. #IT-11) into the spinal cord, 48 ng in total. Saporin (Cat. #PR-01) was used as a control. It was found that while erectile function and emission were not affected, the usual rhythmic contractions of the bulbocaveronosus muscle during ejaculation were prevented.
Related Products: SSP-SAP (Cat. #IT-11), Saporin (Cat. #PR-01)
Talman WT, Nitschke Dragon D, Jones S, Moore SA, Lin L-H (2011) Cardiovascular dysfunction and cardiac injury result from selective glial damage in the nucleus tractus solitarii. Neuroscience 2011 Abstracts 664.14. Society for Neuroscience, Washington, DC.
Summary: In man, extensive CNS dysfunction as may occur after subarachnoid hemorrhage may lead to cardiac damage and cardiac arrhythmias. We have shown that highly selective and restricted lesions of the nucleus tractus solitarii (NTS) may lead to similar cardiac and cardiovascular compromise. For example, using conjugates including the cytotoxin saporin (SAP) to selectively damage NTS neurons that express NK1 receptors or those that express tyrosine hydroxylase (TH) leads to cardiac dysfunction and associated lability of arterial pressure. In continuing efforts to better characterize cellular changes produced by introducing into the NTS conjugates containing SAP, we have studied the effect of anti-dopamine-beta-hydroxylase (anti-DBH)-SAP, stabilized substance P (SSP)-SAP, SAP (unconjugated), blank-SAP (non-targeted peptide conjugate), IgG-SAP (non-targeted immunoglobulin conjugate), and 6-hydoxydopamine (6-OHDA) as a control without SAP injected into NTS. We assessed effects of the injected agents both on cellular markers [NMDAR1 (NMDA receptor subunit 1), GluR2 (AMPA receptor subunit 2), gamma-aminobutyric acid (GABA) receptor type a and b, neuronal nitirc oxide synthase (nNOS), TH, vesicular glutamate transporters (VGluTs), choline acetyl transferase (ChAT), glial fibrillary acidic protein (GFAP), connexin 43 (Cx43), DBH and protein gene product 9.5 (PGP 9.5)] and on cardiovascular and cardiac function. We have found that each compound containing SAP (including blank-SAP, IgG-SAP, unconjugated SAP) led to loss of GFAP and Cx43 immunofluorescent labeling in the NTS as well as lability of arterial pressure, cardiac arrhythmias, and cardiac myocytolysis. Those outcomes occurred despite neuronal specificity for each of the SAP conjugates. For example, anti-DBH-SAP led to a decrease in TH and DBH staining as well as a profound loss in GFAP and Cx43. In contrast, SSP-SAP led to loss of NK1 as well as GFAP, Cx43, and glutamate receptor markers but did not lead to loss of DBH or GABA. SSP-SAP also caused a loss in PGP9.5 which was not observed in all other agents. SAP and blank-SAP, on the other hand, led to loss of GFAP and Cx43 while 6-OHDA led to loss of TH and DBH, increased GFAP and decreased Cx-43. We are still investigating the effects of 6-OHDA on lability of arterial pressure and cardiac events but preliminary data suggest that, in doses used, it led to loss of TH and DBH but did not lead to either lability or cardiac events that were seen with each of the conjugates containing an SAP moiety. This study suggests that glial dysfunction may alone interefere with cardiovascular control through the NTS and may lead to cardiac damage and cardiovascular dysfunction.
Related Products: Anti-DBH-SAP (Cat. #IT-03), SSP-SAP (Cat. #IT-11), Mouse IgG-SAP (Cat. #IT-18), Blank-SAP (Cat. #IT-21), Saporin (Cat. #PR-01)
Ritter S, Li A-J, Wang Q, Dinh TT (2011) Basal metabolic substrate utilization is altered by lesion of hindbrain catecholamine neurons that innervate the medial hypothalamus and substrate selection during glucoprivation is impaired. Neuroscience 2011 Abstracts 88.05. Society for Neuroscience, Washington, DC.
Summary: Central injection of the targeted immunotoxin, anti-dopamine beta hydroxylase (DBH)-saporin (DSAP), retrogradely and selectively lesions norepinephrine (NE) and epinephrine (E) neurons with projections to the injection site. Previous work has shown that DSAP injections targeting the hypothalamic paraventricular nucleus eliminate key counterregulatory responses to acute glucose deficit, including feeding and corticosterone secretion. To examine the role of these NE an E neurons in metabolic control under basal conditions, we injected rats in the PVH with DSAP or control unconjugated saporin (SAP) and analyzed their metabolic profiles using metabolic chambers (Columbus Instruments). Rats were maintained on a standard pelleted rodent diet. We found that the respiratory exchange ratio (RER) was consistently elevated in DSAP rats across the entire circadian cycle under basal conditions, compared to the RER of SAP controls, indicating increased dependence on carbohydrate utilization. Metabolic rate and activity did not differ between groups. This result suggests a chronic enhancement of glucose mobilization or an impairment of the ability to mobilize fatty acids in the DSAP rats. We also found that when challenged by 2-deoxy-D-glucose induced glucoprivation, SAP controls exhibited a rapid decrease in RER, indicating a switch to fat metabolism, whereas DSAP rats did not exhibit this response. Together these results favor the possibility that a central mechanism for fat mobilization is impaired in DSAP rats and that this impairment is reflected under both basal and glucoprivic conditions. The previously reported observation that PVH DSAP-injected rats exhibit a slowly-developing obesity also supports this possibility. Additional findings suggest that this impairment may be due to the loss of NE/E control of corticosterone secretion in the DSAP rats.
Related Products: Anti-DBH-SAP (Cat. #IT-03), , Saporin (Cat. #PR-01)
Histaminergic regulation of seasonal metabolic rhythms in Siberian hamsters.
I’anson H, Jethwa PH, Warner A, Ebling FJ (2011) Histaminergic regulation of seasonal metabolic rhythms in Siberian hamsters. Physiol Behav 103(3-4):268-278. doi: 10.1016/j.physbeh.2011.02.035
Summary: The role of central histaminergic mechanisms on seasonal catabolic state was investigated in hamsters. Siberian hamsters received bilateral 3.8-ng injections of orexin-SAP (Cat. #IT-20) into the tuberomammillary posterior hypothalamic region. Saporin (Cat. #PR-01) was used as a control. During long days, lesioned animals displayed higher locomotor activity, greater oxygen intake, and no net weight gain. During shorter days (hibernation) with less activity, lesioned animals did not lose weight. The data indicate that histaminergic neurons are involved in body weight regulation.
Related Products: Orexin-B-SAP (Cat. #IT-20), Saporin (Cat. #PR-01)
Participation of hindbrain AMP-activated protein kinase in glucoprivic feeding.
Li AJ, Wang Q, Ritter S (2011) Participation of hindbrain AMP-activated protein kinase in glucoprivic feeding. Diabetes 60(2):436-442. doi: 10.2337/db10-0352
Summary: Catecholamine neurons innervating the medial hypothalamus are involved in the control of glucoprivic feeding as well as other responses to glucose deficit. Rats received bilateral 82-ng injections of anti-DBH-SAP (Cat. #IT-03) into the paraventricular hypothalamic nucleus. Saporin (Cat. #PR-01) was used as a control. Lesioned animals did not respond to the administration of a competitive glucose inhibitor, nor did they display phosphorylation of pAMPKα, suggesting that AMPK may be part of a glucose- sensing mechanism.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Contribution of limbic norepinephrine to cannabinoid-induced aversion.
Carvalho AF, Reyes AR, Sterling RC, Unterwald E, Van Bockstaele EJ (2010) Contribution of limbic norepinephrine to cannabinoid-induced aversion. Psychopharmacology (Berl) 211(4):479-491. doi: 10.1007/s00213-010-1923-7
Summary: The authors used bilateral injections of anti-DBH-SAP (Cat. #IT-03) into the nucleus accumbens and the bed nucleus of the stria terminalis to investigate the role of neuroepinephrine in cannabinoid-induced aversion and anxiety. Lesioned animals received bilateral 52.5 ng-injections of anti-DBH-SAP into the nucleus accumbens or 63 ng into the bed nucleus of the stria terminalis. Saporin (Cat. #PR-01) was used as a control. Lesioned animals displayed reversed aversive behavior, but no change in anxiety-like behavior.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Hindbrain catecholamine neurons modulate the growth hormone but not the feeding response to ghrelin.
Emanuel AJ, Ritter S (2010) Hindbrain catecholamine neurons modulate the growth hormone but not the feeding response to ghrelin. Endocrinology 151(7):3237-3246. doi: 10.1210/en.2010-0219
Summary: In this work the authors investigated the role of hindbrain catecholamine neurons in the response to a gastrointestinal peptide, ghrelin. Rats received 42 ng injections of anti-DBH-SAP (Cat. #IT-03) into the paraventricular nucleus of the hypothalamus. Saporin (Cat. #PR-01) was used as a control. Lesioned animals had a prolonged growth hormone (GH) response to ghrelin administration as compared to controls, but the feeding response was unchanged. The results indicate that ghrelin or GH may be involved with a negative feedback response controlling GH levels.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Lawhorn C, Smith DM, Brown LL (2009) Partial ablation of mu-opioid receptor rich striosomes produces deficits on a motor-skill learning task. Neuroscience 163(1):109-119. doi: 10.1016/j.neuroscience.2009.05.021
Summary: The functional role of basal ganglia striosomes is not well understood. In order to examine these cells in the context of motor behavior the authors injected 8.5 ng of dermorphin-SAP (Cat. #IT-12) into several areas of the striatum of mice (saporin, Cat. #PR-01, was used as a control). The animals were then evaluated in complex motor tasks involving the use of striatal circuitry. Animals receiving dermorphin-SAP showed deficits in specific motor tasks corresponding to the extent of the lesion.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Saporin (Cat. #PR-01)
Zhu J, Xu W, Wang J, Ali SF, Angulo JA (2009) The neurokinin-1 receptor modulates the methamphetamine-induced striatal apoptosis and nitric oxide formation in mice. J Neurochem 111(3):656-668. doi: 10.1111/j.1471-4159.2009.06330.x
Summary: This study examined the role of neurokinin-1 receptors (NK1R) on the methamphetamine-induced apoptosis of striatal neurons. 4 ng of SSP-SAP (Cat. #IT-11) or the control, saporin (Cat. #PR-01), was administered to the striatum of mice. Ablation of NK1R-expressing striatal neurons resulted in a significant reduction of methamphetamine-induced apoptosis. The data suggests that the NK1R circuitry in the striatum may be a target for treatment of methamphetamine abuse.
Related Products: SSP-SAP (Cat. #IT-11), Saporin (Cat. #PR-01)
Cao F, Chen SS, Yan XF, Xiao XP, Liu XJ, Yang SB, Xu AJ, Gao F, Yang H, Chen ZJ, Tian YK (2009) Evaluation of side effects through selective ablation of the mu opioid receptor expressing descending nociceptive facilitatory neurons in the rostral ventromedial medulla with dermorphin-saporin. Neurotoxicology 30(6):1096-1106. doi: 10.1016/j.neuro.2009.06.004
Summary: Selective ablation of rostral ventromedial (RVM) neurons expressing mu opioid receptors has been suggested as a treatment for pathological pain. This work investigated the side effects of a 0.5 µg injection of dermorphin-SAP (Cat. #IT-12) into the RVM. Saporin (Cat. #PR-01) was used as a control. Lesioned animals experienced a temporary increase in heart rate and systolic blood pressure, and mild microglial responses, but even these soon returned to normal. The data suggest this system has potential as a target for pain therapeutics.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Saporin (Cat. #PR-01)
Ablation of least shrew central neurokinin NK1 receptors reduces GR73632-induced vomiting.
Ray AP, Chebolu S, Ramirez J, Darmani NA (2009) Ablation of least shrew central neurokinin NK1 receptors reduces GR73632-induced vomiting. Behav Neurosci 123:701-706. doi: 10.1037/a0015733
Summary: In this work the authors investigated the role of central and peripheral nervous systems components that mediate the emetic reflex. Least shrews received an 600-ng injection of SSP-SAP (Cat. #IT-11) into the lateral ventricle. Some animals also received a 4.8-µg intraperitoneal injection of SSP-SAP. Blank-SAP (Cat. #IT-21) and unconjugated saporin (Cat. #PR-01) were used as controls. Lesioned animals displayed reduced emesis, but the data indicate that a minor peripheral nervous system component is also present.
Related Products: SSP-SAP (Cat. #IT-11), Blank-SAP (Cat. #IT-21), Saporin (Cat. #PR-01)
Tronson NC, Schrick C, Guzman YF, Huh KH, Srivastava DP, Penzes P, Guedea AL, Gao C, Radulovic J (2009) Segregated populations of hippocampal principal CA1 neurons mediating conditioning and extinction of contextual fear. J Neurosci 29:3387-3394. doi: 10.1523/JNEUROSCI.5619-08.2009
Summary: This work examines what cell groups are responsible for controlling contextual fear. 180 ng of mu p75-SAP (Cat. #IT-16) was injected into the medial septum of mice. Saporin (Cat. #PR-01) was used as a control. In lesioned animals, fear extinction was lost along with the cholinergic input from the medial septum, while fear conditioning was left intact.
Related Products: mu p75-SAP (Cat. #IT-16), Saporin (Cat. #PR-01)
Rivat C, Vera-Portocarrero LP, Ibrahim MM, Mata HP, Stagg NJ, De Felice M, Porreca F, Malan TP (2009) Spinal NK-1 receptor-expressing neurons and descending pathways support fentanyl-induced pain hypersensitivity in a rat model of postoperative pain. Eur J Neurosci 29:727-737. doi: 10.1111/j.1460-9568.2009.06616.x
Summary: Opioids activate hyperalgesia and allodynia. The authors test the hypothesis that NK-1 receptor-containing ascending pathways play a role in sensitivity to fentanyl. Rats received an intrathecal injection of SP-SAP (Cat. #IT-07), and controls received saporin (Cat. #PR-01). The data indicate that these ascending pathways have a role in fentanyl-induced hyperalgesia.
Related Products: SP-SAP (Cat. #IT-07), Saporin (Cat. #PR-01)
Zhang W, Gardell S, Zhang D, Xie JY, Agnes RS, Badghisi H, Hruby VJ, Rance N, Ossipov MH, Vanderah TW, Porreca F, Lai J (2009) Neuropathic pain is maintained by brainstem neurons co-expressing opioid and cholecystokinin receptors. Brain 132:778-787. doi: 10.1093/brain/awn330
Summary: It has been hypothesized that a subset of rostral ventromedial medulla (RVM) neurons co-expressing the cholecystokinin type 2 receptor and the mu-opioid receptor are responsible for the maintenance of neuropathic pain. Rats were treated with 50-ng bilateral RVM injections of Dermorphin-SAP (Cat. #IT-12), CCK-SAP (Cat. #IT-31), or saporin (Cat. #PR-01) as a control. Lesion of the RVM neurons prevented hyperalgesia in response to CCK treatment, and shortened abnormal pain states caused by sciatic nerve injury.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), CCK-SAP (Cat. #IT-31), Saporin (Cat. #PR-01)
Bee LA, Dickenson AH (2008) Descending facilitation from the brainstem determines behavioural and neuronal hypersensitivity following nerve injury and efficacy of pregabalin. Pain 140:209-223. doi: 10.1016/j.pain.2008.08.008
Summary: Rostral ventromedial medulla (RVM) facilitatory On cells are thought to be involved in the mechanisms that control chronic pain. Dermorphin-SAP (Cat. #IT-12, 3 pmol injected into the RVM of rats) was used to examine how mu-opioid receptor expressing facilitatory cells fit into this circuit. Saporin (Cat. #PR-01) was used as a control. The results show that activity in the RVM may influence the outcome of nerve injury.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Saporin (Cat. #PR-01)
Renal sympathoinhibition induced by hypernatremia: Involvement of A1 noradrenergic neurons.
Pedrino GR, Rosa DA, Korim WS, Cravo SL (2008) Renal sympathoinhibition induced by hypernatremia: Involvement of A1 noradrenergic neurons. Auton Neurosci 142(1-2):55-63. doi: 10.1016/j.autneu.2008.06.006
Summary: A1 noradrenergic neurons in the caudal ventrolateral medulla (CVLM) are thought to contribute to body fluid homeostasis and cardiovascular regulation. In order to examine the role these neurons play on inhibition of renal sympathetic nerve activity (RSNA) induced by hypertonic saline infusion, rats received 6.3 ng of anti-DBH-SAP (Cat. #IT-03) into the CVLM. Saporin (Cat. #PR-01) was used as a control. Animals treated with anti-DBH-SAP displayed lengthened duration of the pressor response and sustained RSNA.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Lesions of medullary catecholaminergic neurons increase salt intake in rats.
Colombari DS, Pedrino GR, Freiria-Oliveira AH, Korim WS, Maurino IC, Cravo SL (2008) Lesions of medullary catecholaminergic neurons increase salt intake in rats. Brain Res Bull 76:572-578. doi: 10.1016/j.brainresbull.2008.04.001
Summary: Catecholaminergic neurons in the caudal ventrolateral medulla (CVLM) are thought to contribute to cardiovascular regulation and body fluid homeostasis. Bilateral 6.3-ng injections of anti-DBH-SAP (Cat. #IT-03) were administered to the CVLM of rats. Saporin (Cat. #PR-01) was used as a control. After lesioning and challenge with either furosemide/captopril or water deprivation, intake of 0.3 M NaCl and water were observed. The data indicate medullary catecholaminergic neurons play an inhibitory role in sodium appetite.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Unilateral ablation of preBotzinger Complex disrupts breathing during sleep but not wakefulness.
McKay LC, Feldman JL (2008) Unilateral ablation of preBotzinger Complex disrupts breathing during sleep but not wakefulness. Am J Respir Crit Care Med 178(1):89-95. doi: 10.1164/rccm.200712-1901OC
Summary: Previous data has shown that ablation of preBötzinger complex (preBötC) neurokinin 1 expressing (NK1R) neurons disrupts breathing patterns in both sleep and wakefulness. The initial disruption is during sleep, with the eventual onset of ataxic breathing while the animals are awake. Here rats received a unilateral injection of SP-SAP (Cat. #IT-07, 6.7 ng) into the left preBötC. SP plus unconjugated saporin (Cat. #PR-01) was used as a control. Unilaterally treated rats did not develop disrupted breathing patterns during wakefulness.
Related Products: SP-SAP (Cat. #IT-07), Saporin (Cat. #PR-01)
IB4 afferent sprouting contributes to bladder dysfunction in spinal rats.
Zinck ND, Downie JW (2008) IB4 afferent sprouting contributes to bladder dysfunction in spinal rats. Exp Neurol 213:293-302. doi: 10.1016/j.expneurol.2008.06.006
Summary: Spinal cord injury can cause inefficient bladder function, but the direct cause is not well understood. Most work has focused on afferent neurons that contain CGRP and respond to NGF. Here the authors investigate the role of isolectin B4 (IB4)-expressing neurons that are supported by GDNF. Rats received intrathecal injections of either 2.4 µg IB4-SAP (Cat. #IT-10) or 3 µg control saporin (Cat. #PR-01). The data suggest that IB4-afferent sprouting is involved in bladder dysfunction following spinal cord transection.
Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)
Darmani NA, Wang Y, Abad J, Ray AP, Thrush GR, Ramirez J (2008) Utilization of the least shrew as a rapid and selective screening model for the antiemetic potential and brain penetration of substance P and NK1 receptor antagonists. Brain Res 1214:58-72. doi: 10.1016/j.brainres.2008.03.077
Summary: This work investigated the role of central tachykinin NK1 receptors in delayed phase vomiting caused by chemotherapeutics. Least shrews received 1.2 mg/kg intraperitoneal injections of SSP-SAP (Cat. #IT-11). Saporin (Cat. #PR-01) and blank-SAP (Cat. #IT-21) were used as controls. In response to administration of a NK1 receptor agonist lesioned animals vomited less than the control group, indicating an important role for NK1 receptors in emesis.
Related Products: SSP-SAP (Cat. #IT-11), Saporin (Cat. #PR-01), Blank-SAP (Cat. #IT-21)
Siva AC, Wild MA, Kirkland RE, Nolan MJ, Lin B, Maruyama T, Yantiri-Wernimont F, Frederickson S, Bowdish KS, Xin H (2008) Targeting CUB domain-containing protein 1 with a monoclonal antibody inhibits metastasis in a prostate cancer model. Cancer Res 68:3759-3766. doi: 10.1158/0008-5472.CAN-07-1657
Summary: CUB domain-containing protein 1 (CDCP1) is an antigen expressed on several metastatic cancers, as well as on CD34+ and CD133+ myeloid leukemic blast cells. After demonstrating in vitro activity of the monoclonal antibody 25A11 with Mab-ZAP (Cat. #IT-04) and Hum-ZAP (Cat. #IT-22) the authors had a custom conjugation of 25A11 and saporin made for testing in mice. Goat-IgG-SAP (Cat. #IT-19) was used as a control for in vivo experiments, and saporin (Cat. #PR-01) was the control in vitro. The direct conjugate significantly inhibited tumor growth as well as metastasis in vivo.
Related Products: Mab-ZAP (Cat. #IT-04), Hum-ZAP (Cat. #IT-22), Goat IgG-SAP (Cat. #IT-19), Saporin (Cat #PR-01)
Rahman W, Suzuki R, Hunt SP, Dickenson AH (2008) Selective ablation of dorsal horn NK(1) expressing cells reveals a modulation of spinal alpha2-adrenergic inhibition of dorsal horn neurones. Neuropharmacology 54:1208-1214. doi: 10.1016/j.neuropharm.2008.03.014
Summary: In this work the spinal origin of the major descending noradrenergic inhibitory pathway is examined with the help of SP-SAP (Cat. #IT-07). Rats received a 10-µl infusion of 1-mM SP-SAP (saporin, Cat. #PR-01, was used as a control) into the sub-arachnoid space terminating in the L4-5 region. Results from examining neuronal responses under the influence of the alpha2-adrenoceptor antagonist atipamezole suggest that NK1 expressing cells are involved with activity in noradrenergic pathways and descending facilitation.
Related Products: SP-SAP (Cat. #IT-07), Saporin (Cat. #PR-01)
Joseph EK, Chen X, Bogen O, Levine JD (2008) Oxaliplatin acts on IB4-positive nociceptors to induce an oxidative stress-dependent acute painful peripheral neuropathy. J Pain 9:463-472. doi: 10.1016/j.jpain.2008.01.335
Summary: Oxaliplatin is a platinum-based chemotherapy agent. Use of this reagent produces various pathological pain states, depending on the dosage site. The authors administered 3.2-µg intrathecal injections of IB4-SAP (Cat. #IT-10), using saporin (Cat. #PR-01) as a control. Lesioning IB4-binding neurons in the dorsal horn completely prevented oxaliplatin-induced hyperalgesia, indicating that the IB4-positive nociceptor neuronal subset is crucial to this type of neuropathy.
Related Products: Saporin (Cat. #PR-01), IB4-SAP (Cat. #IT-10)
Kline IV RH, Wiley RG (2008) Spinal mu-opioid receptor-expressing dorsal horn neurons: role in nociception and morphine antinociception. J Neurosci 28:904-913. doi: 10.1523/JNEUROSCI.4452-07.2008
Summary: The authors used Dermorphin-SAP (Cat. #IT-12) to investigate the function of spinal cord mu-opioid receptor (MOR)-expressing dorsal horn neurons in nociception and morphine analgesia. Rats were treated with 500 ng intrathecal injections of Dermorphin-SAP; 500 ng of Blank-SAP (Cat. #IT-21), and up to 1 µg of Saporin (Cat. #PR-01) were used as controls. The data indicate that MOR-expressing dorsal horn neurons are necessary for morphine action and play a role in nocifensive responses to persistent pain in the formalin test.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Blank-SAP (Cat. #IT-21), Saporin (Cat. #PR-01)
Daniels TR, Ng PP, Delgado T, Lynch MR, Schiller G, Helguera G, Penichet ML (2007) Conjugation of an anti transferrin receptor IgG3-avidin fusion protein with biotinylated saporin results in significant enhancement of its cytotoxicity against malignant hematopoietic cells. Mol Cancer Ther 6:2995-3008. doi: 10.1158/1535-7163.MCT-07-0330
Summary: The human transferrin receptor (hTfR) is overexpressed in malignant cells. Using Advanced Targeting System’s custom biotinylation service, the authors combined an anti-hTfR antibody-avidin fusion protein with biotinylated saporin (Cat. #PR-01, saporin alone), and examined the effect of the combined complex on cancer cells in vitro. Although the antibody-avidin fusion protein has an intrinsic cytotoxic effect, the fusion protein-saporin complex was able to eliminate the population of cells that showed resistance to the fusion protein alone.
Related Products: Saporin (Cat. #PR-01)
Khan IM, Wart CV, Singletary EA, Stanislaus S, Deerinck T, Yaksh TL, Printz MP (2008) Elimination of rat spinal substance P receptor bearing neurons dissociates cardiovascular and nocifensive responses to nicotinic agonists. Neuropharmacology 54(2):269-279. doi: 10.1016/j.neuropharm.2007.09.014
Summary: Nocifensive behavior and cardiovascular responses due to nicotinic agonists may be sustained by substance P-positive primary afferents. Rats received 10-µl intrathecal injections of 10 µM SP-SAP (Cat. #IT-07); unconjugated saporin (Cat. #PR-01) was used as a control. Lesioned animals displayed reduced nocifensive response to nicotinic agonists. Tachycardia and pressor responses were enhanced upon administration of cytisine and epibatidine.
Related Products: Saporin (Cat. #PR-01), SP-SAP (Cat. #IT-07)
Schiltz JC, Sawchenko PE (2007) Specificity and generality of the involvement of catecholaminergic afferents in hypothalamic responses to immune insults. J Comp Neurol 502:455-467. doi: 10.1002/cne.21329
Summary: Interleukin-1 (IL-1) is one of the cytokines that mediates interactions between the immune system and the central nervous system. 380-ng injections of anti-DBH-SAP (Cat. #IT-03) were made into the paraventricular nucleus (PVH) of rats. Saporin (Cat. #PR-01) and mouse IgG-SAP (Cat. #IT-18) were used as controls. Lesioned animals demonstrated reduced responses to administration of IL-1, but restraint stress responses were left intact. The data suggest that ascending catecholaminergic projections mediate PVH response to IL-1.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01), Mouse IgG-SAP (Cat. #IT-18)
Pascual J, Heinrichs SC (2007) Olfactory neophobia and seizure susceptibility phenotypes in an animal model of epilepsy are normalized by impairment of brain corticotropin releasing factor. Epilepsia 48:827-833. doi: 10.1111/j.1528-1167.2007.01024.x
Summary: Olfactory recognition has been linked to epilepsy in behavioral phenotype models. This work examines the role brain stress neuropeptides play in the manifestation of neurological perturbations. Mice were injected with 2 µg/5 µl of CRF-SAP (Cat. #IT-13) into the lateral ventricle. Saporin (Cat. #PR-01) was used as a control. The lesioned mice displayed a temporary reduction in seizure susceptibility, and the reversal of olfactory deficits towards the detection of food.
Related Products: CRF-SAP (Cat. #IT-13), Saporin (Cat. #PR-01)
Vera-Portocarrero LP, Zhang ET, King T, Ossipov MH, Vanderah TW, Lai J, Porreca F (2007) Spinal NK-1 receptor expressing neurons mediate opioid-induced hyperalgesia and antinociceptive tolerance via activation of descending pathways. Pain 129:35-45. doi: 10.1016/j.pain.2006.09.033
Summary: Administration of opioids can induce hyperalgesia in humans and other mammals. In this work the authors examined the role of NK-1 receptor-expressing neurons in the spinal dorsal horn during a hyperalgesic condition not induced by tissue injury. 5 µl of 10 µM SP-SAP (Cat. #IT-07) was injected into the intrathecal space of rats. Saporin (Cat. #PR-01) was used as a control. Osmotic pumps then delivered morphine. Data from the lesioned animals indicate that NK-1 receptor-expressing neurons play a critical role in this hyperalgesic circuit.
Related Products: SP-SAP (Cat. #IT-07), Saporin (Cat. #PR-01)
Abdala AP, Schoorlemmer GH, Colombari E (2006) Ablation of NK(1) receptor bearing neurons in the nucleus of the solitary tract blunts cardiovascular reflexes in awake rats. Brain Res 1119(1):165-173. doi: 10.1016/j.brainres.2006.08.059
Summary: Cardiovascular function is largely controlled by the nucleus of the tractus solitarius (NTS). This work focuses on the baroreflex, cardiopulmonary chemoreflex, and arterial chemoreflex. Rats were injected with either 20 nl of 2 µM SP-SAP (Cat. #IT-07) into the subpostremal NTS, or 200 nl into the subpostremal and commissural NTS. Saporin (Cat. #PR-01) was used as a control. Using various testing methods it was established that NK-1 receptor-expressing neurons in the NTS are critical for these reflexes.
Related Products: SP-SAP (Cat. #IT-07), Saporin (Cat. #PR-01)
Keener WK, Rivera VR, Young CC, Poli MA (2006) An activity-dependent assay for ricin and related RNA N-glycosidases based on electrochemiluminescence. Anal Biochem 357(2):200-207. doi: 10.1016/j.ab.2006.07.005
Summary: The authors use synthetic biotinylated RNA substrates to assay adenine-specific RNA N-glycosidases, one of which is saporin (Cat. #PR-01). The RNA substrates are annealed to a ruthenylated oligodeoxynucleotide, allowing the capture of ruthenium chelate on magnetic beads. The N-glycosidase activity can then be detected by enzyme-linked chemiluminescence. The developed assay provides a robust method for assessing threats involving N-glycosidases.
Related Products: Saporin (Cat. #PR-01)
Bugarith K, Dinh TT, Li AJ, Speth RC, Ritter S (2006) Featured Article: Basomedial hypothalamic injections of neuropeptide Y conjugated to saporin selectively disrupt hypothalamic controls of food intake. Targeting Trends 7(4)
Related Products: Anti-DBH-SAP (Cat. #IT-03), NPY-SAP (Cat. #IT-28), Saporin (Cat. #PR-01), Blank-SAP (Cat. #IT-21)
Read the featured article in Targeting Trends.
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Rygh LJ, Suzuki R, Rahman W, Wong Y, Vonsy JL, Sandhu H, Webber M, Hunt S, Dickenson AH (2006) Local and descending circuits regulate long-term potentiation and zif268 expression in spinal neurons. Eur J Neurosci 24(3):761-772. doi: 10.1111/j.1460-9568.2006.04968.x
Summary: Long-term potentiation (LTP) has been shown to occur in sensory areas of the spinal cord. This modification of synaptic strength may be one of the mechanisms by which acute pain is transformed into chronic pain. 10 µl of 1-µM SP-SAP (Cat. #IT-07) or control saporin (Cat. #PR-01) was injected into the subarachnoid space (L4-L5) of rats. Using electrophysiological recording, immunohistochemistry, behavioral assessment, and antisense experiments, the authors demonstrate that dorsal horn neuron generation of LTP may transform acute pain into chronic pain.
Related Products: SP-SAP (Cat. #IT-07), Saporin (Cat. #PR-01)
Vera-Portocarrero LP, Zhang ET, Ossipov MH, Xie JY, King T, Lai J, Porreca F (2006) Descending facilitation from the rostral ventromedial medulla maintains nerve injury-induced central sensitization. Neuroscience 140(4):1311-1320. doi: 10.1016/j.neuroscience.2006.03.016
Summary: Rats were treated with 1.5 pmol of dermorphin-SAP (Cat. #IT-12) or saporin (Cat. #PR-01) into each side of the rostral ventromedila medulla, followed by spinal nerve ligation. The data indicate that mu opioid-expresing neurons are necessary to maintain nerve injury-induced central sensitization.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Saporin (Cat. #PR-01)
Featured Article: Safety and efficacy of Substance P-SAP
Allen JW (2006) Featured Article: Safety and efficacy of Substance P-SAP. Targeting Trends 7(3)
Related Products: SP-SAP (Cat. #IT-07), Saporin (Cat. #PR-01)
Read the featured article in Targeting Trends.
See Also:
Li AJ, Wang Q, Ritter S (2006) Differential responsiveness of dopamine-beta-hydroxylase gene expression to glucoprivation in different catecholamine cell groups. Endocrinology 147(7):3428-3434. doi: 10.1210/en.2006-0235
Summary: This work examines how subpopulations of hindbrain catecholaminergic neurons participate in systemic glucoregulation. Rats were treated with bilateral 42 ng infusions of anti-DBH-SAP (Cat. #IT-03) into the paraventricular nucleus of the hypothalamus. Dopamine-beta-hydroxylase (DBH) expression in glucoprivic animals was then analyzed by in situ hybridization and immunohistochemistry. The data demonstrate that the ventrolateral medulla contains most of the catecholamine neurons responsive to glucoprivation.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Prenatal glucocorticoid exposure affects learning and vulnerability of cholinergic neurons.
Emgard M, Paradisi M, Pirondi S, Fernandez M, Giardino L, Calza L (2007) Prenatal glucocorticoid exposure affects learning and vulnerability of cholinergic neurons. Neurobiol Aging 28(1):112-121. doi: 10.1016/j.neurobiolaging.2005.11.015
Summary: Women at risk of preterm delivery are commonly treated with synthetic glucocorticoids such as dexamethasone and betamethasone. Here the authors examined adult rats that were prenatally exposed to glucocorticoids. After 2.5 µg intracerebroventricular injections of 192-IgG-SAP (Cat. #IT-01) or 0.44 µg of saporin (Cat. #PR-01), the rats were tested in a water maze pool. The evidence suggests that not only do prenatal glucocorticoids affect adult cognitive function, they also make cholinergic neurons more susceptible to challenges later in life.
Related Products: 192-IgG-SAP (Cat. #IT-01), Saporin (Cat. #PR-01)
Vago R, Marsden CJ, Lord JM, Ippoliti R, Flavell DJ, Flavell SU, Ceriotti A, Fabbrini MS (2005) Saporin and ricin A chain follow different intracellular routes to enter the cytosol of intoxicated cells. FEBS J 272(19):4983-4995. doi: 10.1111/j.1742-4658.2005.04908.x
Summary: Some bacterial toxins such as Pseudomonas aeruginosa exotoxin A carry a KDEL-like C-terminal peptide sequence, which targets the protein to the endoplasmic reticulum. Saporin (Cat. #PR-01) is a plant ribosome-inactivating protein, which does not contain a KDEL-like sequence. Here the authors examined the intracellular pathways utilized by saporin. Although ricin, another plant ribosome-inactivating protein, could be visualized in the Golgi complex, saporin was not. The data suggest that saporin may utilize endosomes during its journey through the cell.
Related Products: Saporin (Cat. #PR-01)
Hodges MR, Opansky C, Qian B, Davis S, Bonis J, Bastasic J, Leekley T, Pan LG, Forster HV (2004) Transient attenuation of CO2 sensitivity after neurotoxic lesions in the medullary raphe-area in awake goats. J Appl Physiol 97(6):2236-2247. doi: 10.1152/japplphysiol.00584.2004
Summary: The authors wished to investigate the influence medullary raphe-area neurons have on breathing. This control may be through CO2/H+ chemoreceptors and/or through non-chemoreceptor modulation. 1 or 10 µl of 50 pM SP-SAP (Cat. #IT-07) or Saporin (Cat. #PR-01) was injected into the raphe of goats. Breathing and CO2 sensitivity were evaluated during different physiologic conditions. The data suggest that SP receptor- and glutamate receptor-expressing neurons in the medullary raphe both influence CO2 sensitivity, but not altered breathing periods.
Related Products: SP-SAP (Cat. #IT-07), Saporin (Cat. #PR-01)
Featured Article: The discovery of saporin
Stirpe F (2004) Featured Article: The discovery of saporin. Targeting Trends 5(3)
Related Products: Saporin (Cat. #PR-01)
Zhang Y, Berger SA (2004) Increased calcium influx and ribosomal content correlate with resistance to endoplasmic reticulum stress-induced cell death in mutant leukemia cell lines. J Biol Chem 279(8):6507-6516. doi: 10.1074/jbc.M306117200
Summary: Ca2+ plays a vital role in many cell processes. To investigate events associated with Ca2+ and endoplasmic reticulum (ER) stress-induced cell death, the authors developed a mutant cell line with resistance to several ER stress-inducing agents. One of the assays used to define the characteristics of this cell line was treatment of the cells with 3 µg/ml of Saporin (Cat. #PR-01) and subsequent analysis of protein expression. The suppression of ribosome function partially reversed the resistance to ER stress-induced cell death.
Related Products: Saporin (Cat. #PR-01)
I'Anson H, Sundling LA, Roland SM, Ritter S (2003) Immunotoxic destruction of distinct catecholaminergic neuron populations disrupts the reproductive response to glucoprivation in female rats. Endocrinology 144(10):4325-4331. doi: 10.1210/en.2003-0258
Summary: The authors hypothesized that hindbrain catcholamine neurons suppressed estrous cycles during chronic glucoprivation as an extension of their role in glucoprivic feeding. 42-ng bilateral injections of anti-DBH-SAP (Cat. #IT-03) were made into the paraventricular nucleus of female rats. Lesioned rats demonstrated inhibition of reproductive function during chronic glucose deficit, but not when a normal amount of glucose was available.
Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)
Waite JJ, Chen AD (2001) Differential changes in rat cholinergic parameters subsequent to immunotoxic lesion of the basal forebrain nuclei. Brain Res 918:113-120. doi: 10.1016/s0006-8993(01)02968-7
Summary: 192-Saporin (Cat. #IT-01) is used extensively to eliminate the cholinergic neurons of the basal forebrain in rats. Waite and Chen compare the degree of loss between 192-Saporin (6 or 8.2 µg in 10 µl into left lateral ventricle) and control (Saporin, 1.82 µg into left lateral ventricle; Cat. #PR-01) using three methods: Assay of post mortem choline acetyltransferase activity, in vivo microdialysis of extracellular acetylcholine (ACh), and in vivo assessment of the rate of ACh synthesis. The infusion of saporin alone had no effect. After fifteen weeks, the authors report compensation of cholinergic activity in lesioned animals occurs in the hippocampus, but not in the frontal cortex as determined by measurement of the rate of ACh synthesis.
Related Products: 192-IgG-SAP (Cat. #IT-01), Saporin Goat Polyclonal (Cat. #AB-15), Saporin Chicken Polyclonal, affinity-purified (Cat. #AB-17AP), Saporin (Cat. #PR-01)
Rajagopal V, Kreitman RJ (2000) Recombinant toxins that bind to the urokinase receptor are cytotoxic without requiring binding to the alpha(2)-macroglobulin receptor. J Biol Chem 275(11):7566-7573. doi: 10.1074/jbc.275.11.7566
Related Products: Saporin (Cat. #PR-01)
Mantyh PW, Rogers SD, Honore P, Allen BJ, Ghilardi JR, Li J, Daughters RS, Lappi DA, Wiley RG, Simone DA (1997) Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor. Science 278:275-279. doi: 10.1126/science.278.5336.275
Related Products: Saporin (Cat. #PR-01), Saporin Chicken Polyclonal, affinity-purified (Cat. #AB-17AP), Saporin Goat Polyclonal (Cat. #AB-15), Saporin Goat Polyclonal, HRP-labeled (Cat. #AB-15HRP), SP-SAP (Cat. #IT-07), Antibody to NK-1 Receptor (Cat. #AB-N04)
Ribosome-inactivating proteins from plants: present status and future prospects.
Stirpe F, Barbieri L, Battelli MG, Soria M, Lappi DA (1992) Ribosome-inactivating proteins from plants: present status and future prospects. Bio/Technol 10:405-412. doi: 10.1038/nbt0492-405
Related Products: Saporin (Cat. #PR-01), Saporin Chicken Polyclonal, affinity-purified (Cat. #AB-17AP), Saporin Goat Polyclonal (Cat. #AB-15), MonoBiotin-ZAP (Cat. #BT-ZAP)
Lappi DA, Esch FS, Barbieri L, Stirpe F, Soria M (1985) Characterization of a Saponaria officinalis seed ribosome-inactivating protein: immunoreactivity and sequence homologies. Biochem Biophys Res Commun 129:934-942. doi: 10.1016/0006-291x(85)91981-3
Related Products: Saporin (Cat. #PR-01), Saporin Chicken Polyclonal, affinity-purified (Cat. #AB-17AP), Saporin Goat Polyclonal (Cat. #AB-15), MonoBiotin-ZAP (Cat. #BT-ZAP)
Stirpe F, Gasperi-Campani A, Barbieri L, Falasca A, Abbondanza A, Stevens WA (1983) Ribosome-inactivating proteins from the seeds of Saponaria officinalis L. (soapwort) of Agrostemma githago L. (corn cockle) and of Asparagus officinalis (asparagus) and from the latex of Hura crepitans L. (sandbox tree). Biochem J 216:617-625. doi: 10.1042/bj2160617
Related Products: Saporin (Cat. #PR-01), Saporin Chicken Polyclonal, affinity-purified (Cat. #AB-17AP), Saporin Goat Polyclonal (Cat. #AB-15), MonoBiotin-ZAP (Cat. #BT-ZAP)