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Adrenergic signalling to astrocytes in anterior cingulate cortex contributes to pain-related aversive memory in rats
Iqbal Z, Lei Z, Ramkrishnan AS, Liu S, Hasan M, Akter M, Lam YY, Li Y (2023) Adrenergic signalling to astrocytes in anterior cingulate cortex contributes to pain-related aversive memory in rats. Commun Biol 6:10. doi: 10.1038/s42003-022-04405-6 PMID: 36604595
Objective: To identify the role of norepinephrine in colorectal distention (sub-threshold for acute pain) induced conditioned place avoidance and plasticity gene expression in the anterior cingulate cortex (ACC).
Summary: The findings suggest that projection-specific adrenergic astrocytic signaling in ACC is integral to system-wide neuromodulation in response to visceral stimuli and plays a key role in mediating pain-related aversion consolidation and memory formation.
Usage: 0.25 ug of Anti-DBH-SAP (1 μg/μl) was injected into each hemisphere of locus coeruleus (LC).
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Towards astroglia-based noradrenergic hypothesis of Alzheimer’s disease
Leanza G, Zorec R (2023) Towards astroglia-based noradrenergic hypothesis of Alzheimer’s disease. Function (Oxf) 4(1):zqac060., IT. doi: 10.1093/function/zqac060 PMID: 36590326
Summary: These results indicate a prominent role of NA-neurons vs. ACh neurons in impairments of working memory, relevant for AD, and are consistent with an astrocyte-specific metabolic impairment in a mouse model of intellectual disability.
Usage: Bilateral icv injection of 192-IgG-SAP and/or Anti-DBH-SAP
Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-DBH-SAP (Cat. #IT-03)
The impact of advanced age on morphine anti-hyperalgesia and the role of mu opioid receptor signaling in the periaqueductal gray of male and female rats
Fullerton E (2022) The impact of advanced age on morphine anti-hyperalgesia and the role of mu opioid receptor signaling in the periaqueductal gray of male and female rats. Georgia State University doi: 10.57709/30509896
Objective: To investigate the impact of advanced age on the antihyperalgesic effect of morphine, as well as its association with changes in μ-opioid receptor expression and binding in the rat midbrain Periaqueductal Gray (PAG) in both male and female rats.
Summary: This study examined the effects of advanced age on the antihyperalgesic properties of morphine and its relationship with mu-opioid receptor expression and binding in the rat midbrain Periaqueductal Gray (PAG). The findings revealed that advanced age attenuated the antihyperalgesic effect of morphine, accompanied by a decrease in mu-opioid receptor expression and binding in the PAG of both male and female rats, suggesting age-related alterations in opioid signaling that may contribute to reduced analgesic efficacy in older individuals.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)
Pituitary adenylate cylase-activating polypeptide receptor: Multiple signaling pathways involved in energy homeostasis
Maunze B (2022) Pituitary adenylate cylase-activating polypeptide receptor: Multiple signaling pathways involved in energy homeostasis. Marquette University Dissertations 1212. Thesis.
Objective: To determine the endogenous role of pituitary adenylate cyclase activating polypeptide (PACAP) in affecting the ventromedial nuclei (VMN) of the hypothalamus and its control of feeding and energy expenditure through the Type I PAC1 receptor (PAC1R).
Summary: VMN cells expressing PAC1 receptors in Male Sprague Dawley rats were knocked down via injection of Saporin or PACAP-SAP and trafficking also pharmacologically inhibited. This increased meal sizes, reduced total number of meals, and induced body weight gain. PACAP signaling replicates the effects of leptin administration in the VMN and appears to enable leptin regulation of energy homeostasis. Co-immunoprecipitation was used to show that VMN PAC1 and leptin receptors are found in the same cell, and they form an immunocomplex. Inhibiting downstream effectors of PACAP signaling, such as PKA and PKC, enhanced or prevented leptin signaling respectively. The current findings revealed that endogenous PACAP signaling in the VMN has a potent regulatory influence over both energy intake in the form of feeding, and energy output via thermogenesis and locomotor activity. Moreover, PACAP actions in the VMN share nearly identical secondary effects as with leptin administration in the same brain region suggesting that these two neuropeptides could functionally intersect.
Related Products: PACAP-SAP (Cat. #IT-84)
The basal forebrain volume reduction detected by MRI does not necessarily link with the cholinergic neuronal loss in the Alzheimer’s disease mouse model
Zhou XA, Ngiam G, Qian L, Sankorrakul K, Coulson EJ, Chuang KH (2022) The basal forebrain volume reduction detected by MRI does not necessarily link with the cholinergic neuronal loss in the Alzheimer’s disease mouse model. Neurobiol Aging 117:24-32. doi: 10.1016/j.neurobiolaging.2022.03.017 PMID: 35640461
Objective: Assess basal forebrain (BF) cholinergic neuron number by histological counts and compare with the volume measurements from an in vivo MRI Alzheimer’s disease (AD) mouse model.
Summary: Degeneration of cholinergic neurons in the BF contributes to cognitive impairment in AD. A decrease of BF volume measured by structural MRI is thought to represent loss of cholinergic neurons. As there are various types of neurons in the BF, whether this MRI measurement actually reflects the change of cholinergic neurons has not been verified. To test whether specific loss of cholinergic neurons results in BF reduction, the authors ablated cholinergic neurons in the Medial septum.
Usage: Lesions were made via injections of mu-p75-SAP (0.5 mg/ml) or control Rabbit-IgG-SAP (0.5 mg/mL) into ten-week-old female C57Bl/6J mice. However, there was no detectable change in MRI volume between lesioned and unlesioned mice. The results indicate that although loss of cholinergic neurons within the BF likely contribute to volume loss, this change in volume cannot be taken as a direct biomarker of cholinergic neuron number.
Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)
Laminarin attenuates ros-mediated cell migration and invasiveness through mitochondrial dysfunction in pancreatic cancer cells
Lee W, Song G, Bae H (2022) Laminarin attenuates ros-mediated cell migration and invasiveness through mitochondrial dysfunction in pancreatic cancer cells. Antioxidants (Basel) 11(9):1714. doi: 10.3390/antiox11091714
Objective: To determine the effects of laminarin on pancreatic cancer.
Summary: Laminarin showed synergistic effects when combined with 5-FU, a standard anticancer agent for pancreatic ductal adenocarcinoma (PDAC) with potential as a treatment for PDAC.
Usage: Lund et al. work on 5-FU resistant EMT-like pancreatic cancer cells are hypersensitive to photochemical internalization of the novel endoglin-targeting immunotoxin Anti-CD105-SAP.
Related Products: Anti-CD105-SAP (Cat. #IT-80)
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Stimulation of the muscarinic receptor M4 activates quiescent neural precursor cells and ameliorates medial septum cholinergic lesion-induced impairments in adult hippocampal neurogenesis
Madrid LI, Bandhavkar S, Hafey K, Jimenez-Martin J, Milne M, Coulson EJ, Jhaveri DJ (2022) Stimulation of the muscarinic receptor M4 activates quiescent neural precursor cells and ameliorates medial septum cholinergic lesion-induced impairments in adult hippocampal neurogenesis. bioRxiv 2022.08.25.505357. doi: 10.1101/2022.08.25.505357
Objective: To investigate the contribution of basal forebrain medial septum (MS) and diagonal band of Broca (DBB) cholinergic neurons that innervate the hippocampus and the identity of the cholinergic receptor(s) that regulate the production and maturation of new neurons.
Summary: This work reveals stage-specific roles of cholinergic signaling in regulating functionally relevant adult hippocampal neurogenesis.
Usage: Medial septum cholinergic lesion was achieved by infusion of mu p75-SAP (0.4 µg/µl). Rabbit IgG-SAP (0.4 µg/µl) was used as control.
Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)
Prenatal exposure to valproic acid causes allodynia associated with spinal microglial activation
Imado E, Sun S, Abawa AR, Tahara T, Kochi T, Huynh TNB, Asano S, Hasebe S, Nakamura Y, Hisaoka-Nakashima K, Kotake Y, Irifune M, Tsuga K, Takuma K, Morioka N, Kiguchi N, Ago Y (2022) Prenatal exposure to valproic acid causes allodynia associated with spinal microglial activation. Neurochem Int 160:105415. doi: 10.1016/j.neuint.2022.105415
Objective: To further understand the mechanism underlying sensory phenotypes in autism spectrum disorder (ASD).
Summary: The authors investigated the age-dependent tactile sensitivity in an animal model of ASD induced by prenatal exposure to valproic acid and subsequently assessed the involvement of microglia in the spinal cord in pain processing.
Usage: To deplete microglia in the spinal cord, Mac-1-SAP (11.2 μg/5.5 μl) was injected intrathecally at the level of L4–L5 in adult (8-week-old) mice.
Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)
Cannabinoid receptors and glial response following a basal forebrain cholinergic lesion
Llorente-Ovejero A, Bengoetxea de Tena I, Martínez-Gardeazabal J, Moreno-Rodríguez M, Lombardero L, Manuel I, Rodríguez-Puertas R (2022) Cannabinoid receptors and glial response following a basal forebrain cholinergic lesion. ACS Pharmacol Transl Sci 5(9):791-802. doi: 10.1021/acsptsci.2c00069 PMID: 36110372
Objective: The endocannabinoid system is involved in the control of learning, memory, and neuroinflammatory processes and plays a role in neurodegeneration, such as in Alzheimer’s disease (AD). The objective was to study the roles of cannabinoid receptors in the regulation of neuroinflammation.
Summary: Selective agonists and antagonists to the cannabinoid receptors CB1 and CB2 were studied for their binding to G-proteins after specific lesioning of the basal forebrain cholinergic neurons (BCFN) using 192-IgG-SAP. These neurons are the same cholinergic pathways that are lost in the early stages of Alzheimer’s disease (AD). In their study, an increase of microglia immunoreactivities (GFAP and Iba-1) and decrease of astrocyte immunoreactivities were seen which indicate microglia-mediated neuroinflammation. In cortical BFCN projection areas, CB1 receptor binding to Gi/o-proteins was upregulated and at the injection site, the area that showed the highest increase of microglia, only slight CB2 binding to Gi/o-proteins were detected. Dose: Rats received 135 ng/μLof 192IgG-saporin (1μL/hemisphere; 0.25μL/min).
Related Products: 192-IgG-SAP (Cat. #IT-01)
Long-term nucleus basalis cholinergic depletion induces attentional deficits and impacts cortical neurons and BDNF levels without affecting the NGF synthesis
Orciani C, Hall H, Pentz R, Foret MK, Do Carmo S, Cuello AC (2022) Long-term nucleus basalis cholinergic depletion induces attentional deficits and impacts cortical neurons and BDNF levels without affecting the NGF synthesis. J Neurochem doi: 10.1111/jnc.15683
Objective: To determine whether reciprocal interaction of basal forebrain cholinergic neurons (BFCN) impact neurotrophin availability and affect cortical neuronal markers.
Summary: There is a neuroprotective role of cholinergic neurotransmission in the adult, fully-differentiated cortex.
Usage: Immunolesioned BFCN projecting mainly to the cortex with 192-IgG-SAP (bilateral 0.5 ug/ul; 1.0 ul/hemisphere) in 2.5 month-old Wistar rats.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Differential role of GABAergic and cholinergic ventral pallidal neurons in behavioral despair, conditioned fear memory and active coping.
Akmese C, Sevinc C, Halim S, Unal G (2022) Differential role of GABAergic and cholinergic ventral pallidal neurons in behavioral despair, conditioned fear memory and active coping. bioRxiv 2022.07.21.500949. doi: 10.1101/2022.07.21.500949
Related Products: 192-IgG-SAP (Cat. #IT-01), GAT1-SAP (Cat. #IT-32)
A century searching for the neurons necessary for wakefulness
Grady FS, Boes AD, Geerling JC (2022) A century searching for the neurons necessary for wakefulness. Front Neurosci 16:930514. doi: 10.3389/fnins.2022.930514
Objective: This review article attempts to summarize research that has investigated the neurons necessary for wakefulness.
Summary: The authors summarize animal experiments and research performed in different brain regions to further understand wakefulness. Several saporin conjugates are discussed.
Usage: Lesions of the basal forebrain were done by injecting a 0.1% solution of either 192-IgG-SAP or Orexin-SAP at four different sites (Fuller et al. and Geraschenko et al.); Intraventricular injection of Anti-DBH-SAP (Gompf et al.); Bilateral injections of 192-IgG-SAP (Kaur et al.).
Related Products: Orexin-B-SAP (Cat. #IT-20)
See Also:
- Fuller P et al. Reassessment of the structural basis of the ascending arousal system. J Comp Neurol 519(5):933-956, 2011.
- Gerashchenko D et al. Insomnia following hypocretin2-saporin lesions of the substantia nigra. Neuroscience 137(1):29-36, 2006.
- Gompf HS et al. Locus ceruleus and anterior cingulate cortex sustain wakefulness in a novel environment. J Neurosci 30(43):14543-14551, 2010.
- Kaur S et al. Effects of ibotenate and 192IgG-saporin lesions of the nucleus basalis magnocellularis/substantia innominata on spontaneous sleep and wake states and on recovery sleep after sleep deprivation in rats. J Neurosci 28:491-504, 2008.
Neuropeptide Toxins
Q: What are neuropeptide-toxins and how do they work?
A: Neuropeptide-toxin conjugates are made up of the ribosome-inactivating protein, saporin, coupled to a naturally-occurring or synthetically-modified neuropeptide such as Substance P or dermorphin. The conjugate has binding specificity similar to the native, unconjugated neuropeptide. When the neuropeptide binds to its cognate receptor, the conjugate is internalized. Once inside the target cell within an endosome, the neuropeptide and saporin separate and some of the saporin translocates into the cytoplasm where it catalytically inactivates ribosomes resulting in cell death.
Q: Are neuropeptide-toxins effective suicide transport agents?
A: The general answer to this question is not currently known. However, in the instance of intrathecally injected dermorphin-SAP (Cat. #IT-12), the evidence does NOT favor suicide transport of the neuropeptide-toxin conjugate. When supramaximal doses of dermorphin-SAP (750 ng) are injected into the lumbar subarachnoid space of adult rats, less than 1% of lumbar dorsal root ganglion cells show evidence of saporin activity. This is in spite of the fact that many of these neurons express the targeted mu opioid receptor on their central terminals in the superficial dorsal horn of the spinal cord. This assertion is based on analysis of over 16,000 neurons from dorsal root ganglia in six rats.
See: Targeted Toxins
Sensory and motor visual functions in Parkinson’s Disease with respect to freezing of gait symptoms
Alhassan M (2022) Sensory and motor visual functions in Parkinson’s Disease with respect to freezing of gait symptoms. J Ophthalmol & Vis Sci 7(2):1069.
Objective: This review article summarizes the results from previous studies focusing on visual functions in Parkinson’s Disease patients.
Summary: Freezing of gait (FOG) is considered to be a motor disorder symptom that affects some Parkinson Disease (PD) patients; however, it is hypothesized that sensory systems may also be involved in FOG. Visual functions include high contrast visual acuity, low contrast visual acuity, contrast sensitivity, Vernier acuity, mesopic vision, stereopsis, motion perception, and vergence eye movements and are all affected in PD patients with FOG patients having more deficits in some of these functions. FOG patients also had impairments in non-dopaminergic mediated functions which suggests greater impairment in two functions that involve cholinergic neurotransmitters. 192-IgG-SAP (Cat. IT-01) was used to create a PD rat animal model to study the contribution of the cholinergic system to motor functions. It was found that the fall rates were more frequent in rats, that were injected with dual 192 IgG-saporin /6-hydroxydopamine (6-OHDA) than rats with either isolated cholinergic or isolated dopaminergic lesions.
Related Products: 192-IgG-SAP (Cat. #IT-01)
See Also:
Mechanism of opioid addiction and its intervention therapy: Focusing on the reward circuitry and mu-opioid receptor
Zhang JJ, Song CG, Dai JM, Li L, Yang XM, Chen ZN (2022) Mechanism of opioid addiction and its intervention therapy: Focusing on the reward circuitry and mu-opioid receptor. MedComm 3(3):e148. doi: 10.1002/mco2.148 PMID: 35774845
Objective: To examine the mechanism of opioid addiction, with a specific focus on the reward circuitry and the role of the mu-opioid receptor, and to explore potential intervention therapies.
Summary: The authors discuss the neurobiological processes underlying addiction and highlight the importance of understanding these mechanisms in developing effective intervention therapies for opioid addiction.
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)
See Also:
Worked to the bone: antibody-based conditioning as the future of transplant biology
Griffin JM, Healy FM, Dahal LN, Floisand Y, Woolley JF (2022) Worked to the bone: antibody-based conditioning as the future of transplant biology. J Hematol Oncol 15(1):65. doi: 10.1186/s13045-022-01284-6
Objective: To analyze the current status of antibody-based drugs in pre-transplant conditioning regimens and assess their potential in the future of transplant biology.
Summary: This review article suggests that antibody-based conditioning regimens may be the next big advancement in hematopoietic stem cell transplantation.
Related Products: Anti-CD117-SAP (Cat. #IT-83)
See Also:
- Palchaudhuri R et al. Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nat Biotechnol 34:738-745, 2016.
- Castiello MC et al. Efficacy and safety of anti-CD45-saporin as conditioning agent for RAG deficiency. J Allergy Clin Immunol 147(1):309-320.e6, 2021.
- Czechowicz A et al. Selective hematopoietic stem cell ablation using CD117-antibody-drug-conjugates enables safe and effective transplantation with immunity preservation. Nat Commun 10:617, 2019.
- Li Z et al. Hematopoietic chimerism and donor-specific skin allograft tolerance after non-genotoxic CD117 antibody-drug-conjugate conditioning in MHC-mismatched allotransplantation. Nat Commun 10:616, 2019.
Neural pathway for gut feelings: vagal interoceptive feedback from the gastrointestinal tract is a critical modulator of anxiety-like behavior
Krieger JP, Asker M, Van der Velden P, Börchers S, Richard JE, Maric I, Longo F, Singh A, De Larigue G, Skibicka KP (2022) Neural pathway for gut feelings: vagal interoceptive feedback from the gastrointestinal tract is a critical modulator of anxiety-like behavior. Biological Psychiatry in press. doi: 10.1016/j.biopsych.2022.04.020
Objective: To determine how the sensing of gastrointestinal state affects anxiety.
Summary: Vagal sensory signals from the gastrointestinal tract are critical for baseline and feeding-induced tuning of anxiety via the central amygdala in rats. The article results suggest vagal gut-brain signaling as a target to normalize interoception in anxiety.
Usage: 1.5 ul of CCK-SAP or Blank-SAP were delivered into each nodose ganglion at 250 ng/ul.
Related Products: CCK-SAP (Cat. #IT-31), Blank-SAP (Cat. #IT-21)
Ablation of dorsomedial striatum patch compartment results in modification to reward-driven behaviors in rats
Ahn JP (2022) Ablation of dorsomedial striatum patch compartment results in modification to reward-driven behaviors in rats. Mercer University School of Medicine Thesis.
Objective: This thesis intended to demonstrate that selective ablation of dorsomedial striatum (DMS) patch compartment neurons results in a significant impact on the initial development of reward-driven behaviors during the early stages of drug seeking behavior.
Summary: Through the use Dermorphin-SAP and training rats to self-administer cocaine, ablation of the patch compartment of the DMS resulted in an increase in early-stage lever pressing, suggesting that the DMS patch compartment contributes to reward-driven behaviors.
Usage: 17 ng/µl Dermorphin-SAP in sterile artificial cerebrospinal fluid (aCSF) to selectively ablate patch compartment neurons. Infusions into either the dorsomedial striatum or dorsolateral striatum (2 µl of infusion liquid).
Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)
Asymmetric activation of microglia in the hippocampus drives anxiodepressive consequences of trigeminal neuralgia
Chen LQ, Lv XJ, Guo QH, Lv SS, Lv N, Yu J, Xu WD, Zhang YQ (2022) Asymmetric activation of microglia in the hippocampus drives anxiodepressive consequences of trigeminal neuralgia. bioRxiv 2022.04.16.488241. doi: 10.1101/2022.04.16.488241
Related Products: Mac-1-SAP rat (Cat. #IT-33)
In vivo effects in mice of an anti-T cell immunotoxin.
Marcucci F, Lappi DA, Ghislieri M, Martineau D, Siena S, Bregni M, Soria M, Gianni AM (1989) In vivo effects in mice of an anti-T cell immunotoxin. J Immunol 142:2955-2960.
Related Products: OX7-SAP (Cat. #IT-02)