targeted-toxins

Shim HS, Park H-J, Lee M-S, Ye M, Shim I (2018) The role of the supramammillary area of the hypothalamus in cognitive functions. Animal Cells and Systems 22:37-44. doi: 10.1080/19768354.2018.1427627

Related Products: 192-IgG-SAP (Cat. #IT-01)

Dobryakova YV, Kasianov A, Zaichenko MI, Stepanichev MY, Chesnokova EA, Kolosov PM, Markevich VA, Bolshakov AP (2018) Intracerebroventricular administration of 192IgG-saporin alters expression of microglia-associated genes in the dorsal but not ventral hippocampus. Front Mol Neurosci 10:429. doi: 10.3389/fnmol.2017.00429

Objective: To analyze the postponed consequences of cholinergic deficit in different parts of the hippocampus.

Summary: Disturbance of memory-associated behavior after administration of 192-IgG-SAP is associated with upregulation of microglia-associated genes in the dorsal but not ventral hippocampus.

Usage: Rats received bilateral i.c.v.infusions of 192-IgG-SAP (4 mcg/site).

Related Products: 192-IgG-SAP (Cat. #IT-01)

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)

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.2017.08.006

Objective: 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)

Ferrari LF, Khomula EV, Araldi D, Levine JD (2018) CD44 signaling mediates high molecular weight hyaluronan-induced antihyperalgesia. J Neurosci 38(2):308-321. doi: 10.1523/JNEUROSCI.2695-17.2017

Objective: To study the role of the cognate hyaluronan receptor, CD44, signaling in anti-hyperalgesia induced by high molecular weight hyaluronan (HMWH).

Summary: These results demonstrate the central role of CD44 signaling in HMWH-induced anti-hyperalgesia, and establish it as a therapeutic target against inflammatory and neuropathic pain.

Usage: Both IB4-SAP and SSP-SAP were diluted in saline to doses previously shown to deplete nonpeptidergic (3.2 mcg/rat for IB4-SAP) and peptidergic (100 ng/rat for SSP-SAP) fibers. The toxins were administered intrathecally, in a volume of 20 mcl, 14 d before intradermal injection of LMWH on the dorsum of the hindpaw. Treatment with either conjugate, or a combination of the two, did not significantly affect mechanical nociceptive threshold.

Related Products: IB4-SAP (Cat. #IT-10), SSP-SAP (Cat. #IT-11), Anti-CD44-SAP (Cat. #IT-72)

Lund K, Olsen CE, Wong JJW, Olsen PA, Solberg NT, Høgset A, Krauss S, Selbo PK (2017) 5-FU resistant EMT-like pancreatic cancer cells are hypersensitive to photochemical internalization of the novel endoglin-targeting immunotoxin CD105-saporin. J Exp Clin Cancer Res 36(1):185.. doi: 10.1186/s13046-017-0662-6

Objective: Investigate resistance mechanisms and photochemical strategies to overcome 5-FU resistance in pancreatic adenocarcinoma.

Summary: Expression of CD105 was investigated using RT-qPCR, western blotting, flow cytometry, and fluorescence microscopy, and co-localization of TPCS2a and Anti-CD105-SAP was assessed using microscopy. MTS assay was used to investigate cytotoxic effects of photochemical internalization of Anti-CD105-SAP. For the first time, we demonstrate the promise of PCI-based targeting of CD105 in site-specific elimination of 5-FU resistant pancreatic cancer cells using Anti-CD105-SAP in vitro. PCI-based targeting of CD105 may represent a potent anti-cancer strategy and should be further evaluated in preclinical models.

Usage: Cells were seeded (3000/well) in 96-well plates and allowed to attach overnight. The cells were incubated with the Anti-CD105-saporin (2.4 nM) or Saporin as a control (6.48 nM; Saporin was added in a molecular ratio of 2.7:1 to the immunotoxin) giving an equal ratio of Saporin to immunotoxin), with or without the photosensitizer TPCS2a (0.35 μg/ml) for 18 h.

Related Products: Anti-CD105-SAP (Cat. #IT-80)

Zhang J, Wang H, Wu S, Liu Q, Wang N (2017) Regulation of reentrainment function is dependent on a certain minimal number of intact functional iprgcs in rd mice. J Ophthalmol 2017:6804853.. doi: 10.1155/2017/6804853

Related Products: Melanopsin-SAP (Cat. #IT-44)

Liu A, Aoki S, Wickens J (2017) A streamlined method for the preparation of gelatin embedded brains and simplified organization of sections for serial reconstructions. Bio-protocol 7(22):e2610.. doi: 10.21769/BioProtoc.2610

Related Products: Anti-ChAT-SAP (Cat. #IT-42)

Horner KA, Logue JB, Jenrette TA (2017) Patch compartment lesions reduce habitual sucrose consumption. Neuroscience 2017 Abstracts 689.16 / II23. Society for Neuroscience, Washington, DC.

Summary: The striatum mediates habit formation and reward association. The striatum can be divided into the patch and matrix compartment, which are two neurochemically and anatomically distinct regions that may sub-serve different aspects of behavior. For example, the patch compartment may mediate reward-related behaviors, while the matrix compartment may mediate adaptive motor functions. Furthermore, previous studies have shown that enhanced relative activation of the patch versus matrix compartment is associated with inflexible behaviors, such as stereotypy. Habitual behaviors are also inflexible in nature, but whether enhanced activation of the patch compartment contributes to habitual behavior is not known. The goal of the current study was to examine the role of patch compartment neurons in the development of habit formation. We used dermorphin-saporin to specifically ablate neurons of the patch compartment prior to training animals to self-administer sucrose on a random interval schedule of reinforcement, which has been shown to foster habit formation. Our data showed that destruction of the neurons of the patch compartment prevented the reinstatement of sucrose self-administration after sucrose devaluation, indicating that absence of the patch compartment interrupted the development of habitual behavior. Our data also indicate that c-Fos levels were decreased in the dorsolateral striatum (DLS) and sensorimotor cortex (SMC), but increased in dorsomedial striatum (DMS) and prefrontal cortex (PFC) in patch-lesioned animals that did not develop habitual behavior, indicating that diminished habit formation is associated with decreased activation of regions that participate in habitual behavior, and increased in regions associated with goal-directed behaviors. Together, these data indicate that the patch compartment participates in habit formation by altering the flow of information through basal ganglia circuits.

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12)

Falquetto B, Oliveira LM, Moreira TS, Takakura AC (2017) Role of orexinergic neurons in the chemosensory control of breathing in a Parkinson’s disease model. Neuroscience 2017 Abstracts 779.08 / HH1. Society for Neuroscience, Washington, DC.

Summary: Parkinson´s disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra compacta (SNpc). Non-motor symptoms such as neuropsychiatric, sleep and breathing disorders are also observed in PD. Previous study has already demonstrated that in 6-hydroxydopamine (6-OHDA)-model of PD there is a reduction in the number of phox2b neurons in the retrotrapezoid nucleus (RTN) and a decrease in the respiratory response to hypercapnia. Here, we tested the involvement of orexin cells from lateral hypothalamus/perifornical area (LH/PeF) on breathing in this model of PD. 6-OHDA (24 µg/µl) injections into the striatum reduced the number of catecholaminergic (40 days: 128 ± 10 and 60 days: 116 ± 13 vs. vehicle: 938 ± 15 neurons) and orexin-B-ir neurons (40 days: 310 ± 9 and 60 days: 258 ± 15 vs. vehicle: 412 ± 13 neurons). The injection of anti-Orexin-B saporin into the LH/PeF produces a further reduction in the number of orexinergic neurons in PD animals (79 ± 8 vs. control: 427 ± 14 neurons). The respiratory frequency (fR) at rest and in response to hypercapnia (7% CO2) was assessed 60 days after bilateral 6-OHDA or vehicle injections into the striatum and anti-Orexin-B saporin or IgG saporin into the LH/PeF during sleep and wakefulness in the dark and light phases of the diurnal cycle. Sixty days after 6-OHDA, we observed a reduction of fR at rest during sleep in the light phase only in PD animals (56 ± 2 vs. control: 66 ± 2 bpm). During the dark phase, there is a reduction in fR response to hypercapnia in PD animals with depletion of orexinergic neurons during wakefulness (119 ± 6 vs. control: 152 ± 3 bpm) and sleep (128 ± 7 vs. control: 147 ± 5 bpm). Our data suggest that orexinergic neurons are important to restore chemoreceptor function in a rat model of PD during sleep and wakefulness in rats.

Related Products: Orexin-B-SAP (Cat. #IT-20)

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