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Characterizing a new tool to manipulate area postrema GLP1R+ neurons across species
Fulton S, Horn CC, Zhang C (2024) Characterizing a new tool to manipulate area postrema GLP1R+ neurons across species. Physiol Behav 114474. doi: 10.1016/j.physbeh.2024.114474 PMID: 38272107
Objective: Characterize the ligand exenatide conjugated to saporin as a tool to ablate GLP1 receptor-expressing cells from human, mice, and shrews, a small animal model capable of emesis (vomiting).
Summary: Nausea is a distressing sensation that is a common side effect of many medications. Nausea and emesis are among the top adverse side effects of glucagon-like peptide-1 (GLP1) receptor (GLP1R) agonists-based medications to treat type 2 diabetes and obesity. The area postrema is a brain structure that mediates nausea effects. The authors provide characterization of Ex4-SAP (GLP-1-SAP) to specifically ablate GLP1R-expressing HEK293T cells in vitro and in area postrema neurons in mice and house musk shrews in vivo.
Usage: C57BL-6J mice were injected with Ex4-SAP (IT-90) or Blank-Streptavidin-SAP at 200 ng/ul, in a total of 400 nl at a rate of 2 nl/second. Musk shrews were injected with Ex4-SAP (IT-90) or Blank-Streptavidin-SAP at 500 ng/ul, in a total of 200 nl at a rate of 2 nl/second.
Related Products: Ex4-SAP (GLP-1-SAP) (Cat. #IT-90), Blank-Streptavidin-SAP (Cat. #IT-27B)
Etonogestrel promotes respiratory recovery in an in vivo rat model of central chemoreflex impairment
Janes TA, Cardani S, Saini JK, Pagliardini S (2024) Etonogestrel promotes respiratory recovery in an in vivo rat model of central chemoreflex impairment. Acta Physiol (Oxf) e14093. doi: 10.1111/apha.14093 PMID: 38258900
Objective: Examine the use of progestins and synthetic progestins in the stimulation of breathing, especially after chemoreflexive impairment.
Summary: Central CO2 chemoreflex is important for respiratory control. The retrotrapezoid nucleus is involved in CO2 chemosensitivity where its removal or inhibition attenuates CO2 chemoreflexes and diminishes restful breathing. Progesterone stimulates restful breathing and CO2 chemoreflexes. The authors investigated whether acute or chronic administration of the progestinic drug, etonogestrel, could help in the recovery of respiratory chemoreflexes following lesion of the retrotrapezoid nucleus via a SP-SAP.
Usage: Rats were injected with 26-43.3 ng/ul of SP-SAP (IT-11) or 46.7 ng/ul of Blank-SAP (IT-21), with 150 nl per injection.
Related Products: SP-SAP (Cat. #IT-07), Blank-SAP (Cat. #IT-21)
A role of frontal association cortex in long-term object recognition memory of objects with complex features in rats
Masmudi-Martín M, López-Aranda MF, Navarro-Lobato I, Khan ZU (2024) A role of frontal association cortex in long-term object recognition memory of objects with complex features in rats. Eur J Neurosci doi: 10.1111/ejn.16243 PMID: 38238909
Objective: Provide evidence that the frontal association cortex and not the Perirhinal cortex is essential for object recognition memory (ORM) of objects with complex features.
Summary: The Perirhinal cortex is a brain area that has been seen as being crucial for ORM. However, the authors challenge that thought by using an ORM enhancer named RGS14414. Used as a tool, expression of it in rat brain frontal association cortex induced the formation of long-term complex ORM whereas the expression of the enhancer in Perirhinal cortex didn’t illicit the same effect. The authors also showed that expression of the enhancer in Perirhinal cortex instead caused formation of ORM of objects with only simple features. Furthermore, the selective elimination of frontal association cortex neurons via OX7-SAP (IT-02) completely removed the formation of complex ORM.
Usage: OX7-SAP (IT-02) was injected into the frontal association cortex of rats at a dose of 0.2 ug in 1 ul.
Related Products: OX7-SAP (Cat. #IT-02)
Regulation of ethanol-mediated dopamine elevation by glycine receptors located on cholinergic interneurons in the nucleus accumbens
Loftén A, Adermark L, Ericson M, Söderpalm B (2023) Regulation of ethanol-mediated dopamine elevation by glycine receptors located on cholinergic interneurons in the nucleus accumbens. Addict Biol 28(12):e13349. doi: 10.1111/adb.13349 PMID: 38017639
Objective: The aim of this study was to explore the role of glycine receptors (GlyRs) on cholinergic interneurons (CIN) in sustaining extracellular dopamine levels and in ethanol-induced dopamine release.
Summary: Alcohol use disorder is one of the major psychiatric disorders worldwide. Ethanol reward is one of the many factors contributing to the disorder. The rewarding and reinforcing properties of ethanol have been linked to activation of the mesolimbic dopamine system, an effect that involves glycine receptors (GlyRs) in the nucleus accumbens. The study suggests that CIN are not important for GlyR-mediated regulation of basal dopamine output, but that CIN ablation blunts the ethanol-induced dopamine release by reducing the release of GlyR agonists.
Usage: CIN were ablated by Anti-ChAT-SAP administered locally in the nucleus accumbens of male Wistar rats. Rabbit-IgG-SAP was used as a control. Microinfusion was performed unilaterally into the nAc at a concentration of 0.5 ug/ul at 0.05 ul/min for 10 min for a total of 0.5 ul.
Related Products: Anti-ChAT-SAP (Cat. #IT-42), Rabbit IgG-SAP (Cat. #IT-35)
Regulation of nociception threshold by norepinephrine through adrenergic α2 receptor in rat models of Parkinson’s disease
Gao Q, Zhang Y, Wang X, Wang R, Zhang L (2023) Regulation of nociception threshold by norepinephrine through adrenergic α2 receptor in rat models of Parkinson’s disease. CNS Neurosci Ther doi: 10.1111/cns.14446 PMID: 37721421
Objective: To investigate the effect of norepinephrine on the activation of brain cells through adrenergic α2 receptor, to regulate the nociception threshold in a 6-OHDA-induced animal model of Parkinson’s disease (PD).
Summary: The change of norepinephrine content can affect the activation of prefrontal and cingulate gyrus glial cells and participate in the regulation of nociception threshold in PD rats. Adrenergic α2 receptor agonist and central presynaptic membrane α2 receptor blocker both affect cell activation and improve hyperalgesia.
Usage: 4 μL of Anti-DBH-saporin was injected into the right lateral ventricle (1.25 μg/μL, 0.9% NaCl dilution), and injected at the rate of 1 μL/min.
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Autonomic nerve and its modulation approaches for heart failure
Zhang H, Zhu Y, Chen S, Deng K, Zheng M, Zeng Z, Wang Q, Cai H, Lu Z (2023) Autonomic nerve and its modulation approaches for heart failure. Brain & Heart doi: 10.36922/bh.0913
Objective: Authors review neural modulation approaches that can assist in the management of heart failure.
Summary: The autonomic nervous system governs the heart’s neurological regulation through opposing functions of its sympathetic and parasympathetic components. Potential treatments for heart failure include inhibiting the sympathetic nerve’s overactivity and restoring parasympathetic activity in the heart. CTB-SAP was used to ablate cardiac sympathetic neurons via retrograde transport on stellate ganglion neurons.
Usage: CTB-SAP was injected into the right superior vervical ganglion of adult male Sprague-Dawley rats (50 ug/rat).
Related Products: CTB-SAP (Cat. #IT-14)
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Mobilization-based engraftment of haematopoietic stem cells: a new perspective for chemotherapy-free gene therapy and transplantation
Canarutto D, Omer Javed A, Pedrazzani G, Ferrari S, Naldini L (2023) Mobilization-based engraftment of haematopoietic stem cells: a new perspective for chemotherapy-free gene therapy and transplantation. Br Med Bull ldad017. doi: 10.1093/bmb/ldad017 PMID: 37460391
Objective: The authors review alternative chemotherapy-free approaches to niche voidance that could replace conventional regimens and alleviate the morbidity of the procedure.
Summary: In haematopoietic stem cell transplantation (HSCT), haematopoietic stem cells (HSCs) from a healthy donor replace the patient’s. Ex vivo HSC gene therapy (HSC GT) is a form of HSCT in which HSCs are genetically modified before infusion, to generate a progeny of gene-modified cells. In HSCT and HSC-GT, chemotherapy is administered before infusion to free space in the bone marrow niche, which is required for the engraftment of infused cells. One approach reviewed by the authors involves Anti-CD45-SAP. The conjugate was shown to clear the white blood cell compartment. Administration into mice prior to HSCT resulted in comparable haematopoietic reconstitution as total body irradiation, with less side effects (Palchaudhuri R. et al, 2016) and faster T-cell repopulation likely due to sparing radio damage to the thymic stroma (Schiroli G et al., 2017).
Related Products: Anti-CD45.2-SAP (Cat. #IT-91)
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.
- Schiroli G et al. Preclinical modeling highlights the therapeutic potential of hematopoietic stem cell gene editing for correction of SCID-X1. Sci Transl Med 9(411):eaan0820, 2017.
Cannabinoids: Emerging sleep modulator
Low ZXB, Lee XR, Soga T, Goh BH, Alex D, Kumari Y (2023) Cannabinoids: Emerging sleep modulator. Biomed Pharmacother 165:115102. doi: 10.1016/j.biopha.2023.115102 PMID: 37406510
Objective: To review the modulation of sleep by cannabinoids and the endocannabinoid system.
Summary: This review article discusses the role of cannabinoids, including endocannabinoids like anandamide and phytocannabinoids like THC and CBD, in regulating the sleep-wake cycle. The authors review evidence that cannabinoids act on areas of the brain involved in promoting sleep, like the ventrolateral preoptic nucleus, and inhibit wake-promoting areas, like the locus coeruleus.
Related Products: Orexin-B-SAP (Cat. #IT-20)
The gut-brain axis mediates bacterial driven modulation of reward signaling
Kim JS, Williams KC, Kirkland RA, Schade R, Freeman KG, Cawthon CR, Rautmann AW, Smith JM, Edwards GL, Glenn TC, Holmes PV, de Lartigue G, de La Serre CB (2023) The gut-brain axis mediates bacterial driven modulation of reward signaling. Mol Metab 26:101764. doi: 10.1016/j.molmet.2023.101764 PMID: 37380023
Objective: To investigate the role of gut microbiota and vagal signaling in modulating brain dopamine reward pathways and appetitive feeding behavior.
Summary: The study found that high-fat diet and transfer of high-fat microbiota to germ-free rats reduced dopamine signaling and motivated feeding behavior compared to chow-fed and low-fat microbiota groups. Vagal deafferentation restored dopamine signaling and feeding motivation in high-fat microbiota rats, indicating gut bacteria signals that dampen reward are vagally mediated.
Usage: Animals were injected bilaterally into the nodose ganglion with either Saporin or CCK-SAP. A pulled glass micropipette containing either CCK-SAP (240 ng/ml in 0.1 M phosphate buffer) or SAP alone was inserted under the sheath of the cervical vagus and into the NG, the injection was done with a pressure-injector into two sites (one proximal and one distal, total volume, 1 µl).
Related Products: CCK-SAP (Cat. #IT-31), Saporin (Cat. #PR-01)
Tongue exercise-induced functional and structural upper airway plasticity in a rodent model of hypoglossal (XII) motor neuron loss
Keilholz A, Homan C, Schroeder A, Osman K, Smith C, Pathak I, Streeter K, Ozden I, Ma L, Lever T, Nichols N (2023) Tongue exercise-induced functional and structural upper airway plasticity in a rodent model of hypoglossal (XII) motor neuron loss. American Physiology Summit 2023 Meeting Abstracts 38(S1)
Objective: Examine if upper airway function/coordination can be improved in lower motor neuron (LMN) degeneration by tongue exercise-induced axis plasticity.
Summary: Tongue muscle weakness in patients with motor neuron diseases suggests a potential role for therapeutic exercise but lacks evidence due to lack of an appropriate model. Data suggests that tongue exercise in CTB-SAP rats results in enhanced XII motor plasticity and mitigates structural airway changes. In conclusion, tongue exercise appears to cause XII-tongue axis plasticity to improve upper airway function and coordination in the face of XII LMN degeneration.
Usage: The authors developed a novel rodent model using intralingual injections of CTB-SAP to induce targeted loss of XII motor neurons and motor output.
Related Products: CTB-SAP (Cat. #IT-14)
Gastric vagal afferent signaling to the basolateral amygdala mediates anxiety-like behaviors in experimental colitis mice
Chen CH, Tsai TC, Wu YJ, Hsu KS (2023) Gastric vagal afferent signaling to the basolateral amygdala mediates anxiety-like behaviors in experimental colitis mice. JCI Insight e161874. doi: 10.1172/jci.insight.161874 PMID: 37200091
Objective: This study aimed to characterize gut-to-brain signaling and brain circuitry responsible for anxiety-like behaviors in a mouse model of inflammatory bowel disease.
Summary: The researchers found that mice with experimental colitis induced by dextran sulfate sodium administration displayed increased anxiety-like behaviors, which were prevented by cutting the vagus nerve connecting the gut to the brain. Further experiments showed that silencing brain cells in the locus coeruleus that project to the basolateral amygdala reduced anxiety behaviors in the colitis mice.
Usage: CCK-SAP (250 ng/µl) or Blank-SAP (250 ng/µl) were unilaterally or bilaterally injected to rostral (0.5 µl) and caudal (0.5 µl) parts of the nodose ganglia using a beveled injection pipette controlled by a microprocessor-controlled injector at the speed of 50 nl/sec.
Related Products: CCK-SAP (Cat. #IT-31), Blank-SAP (Cat. #IT-21)
The effects of loss of orexin neurons on attention
Sainz AE (2023) The effects of loss of orexin neurons on attention. William & Mary Thesis.
Objective: This paper examines the effects of loss of orexin neurons on attention in mice.
Summary: This undergraduate honors thesis from William & Mary tested attention in mice after selective loss of orexin neurons, which are important for arousal. The researchers found impairments in sustained attention and cognitive flexibility in the mice missing orexin neurons.
Usage: 0.5 µl of Orexin-B-SAP (0.4 µg/µl) or saline was administered to both sides of the lateral hypothalamus for 30 seconds using a 1 µl syringe.
Related Products: Orexin-B-SAP (Cat. #IT-20)
The VLM a1/c1 ca/npy neuronal projections to the perifornical area of the lateral hypothalamus and its functional role in glucoprivic feeding
Choi P (2023) The VLM a1/c1 ca/npy neuronal projections to the perifornical area of the lateral hypothalamus and its functional role in glucoprivic feeding. Washington State Univ Thesis.
Objective: This dissertation aimed to determine the role of neuropeptide Y (NPY) receptor signaling from the ventrolateral medulla (VLM) catecholamine (CA) neurons in the lateral hypothalamus (LHA) for glucoprivic feeding.
Summary: The results showed that NPY receptor-expressing neurons in the perifornical area of the LHA are required for glucoprivic feeding evoked by 2-deoxyglucose. Furthermore, antagonism of NPY Y1 or Y2 receptors in the LHA attenuated feeding evoked by chemogenetic activation of VLM CA neurons, indicating NPY release from VLM neurons activates LHA NPY receptors to elicit glucoprivic feeding.
Usage: NPY-SAP (50 ng per 100 nL/site) or control Blank-SAP (50 ng per 100 nL/site) dissolved in 0.01 M phosphate buffer was infused slowly over a 5 minute period directly into the perifornical lateral hypothalamic (stereotaxic coordinate: 2.8 mm caudal from bregma, +/- 1.2 mm lateral to the midline, and -7.4 mm from the dura mater) through a pulled glass capillary pipette (30 µm tip diameter) connected to a Picospritzer. The rats were allowed at least 7 days for a full recovery from surgery and NPY-SAP-induced neuronal ablation.
Related Products: NPY-SAP (Cat. #IT-28), Blank-SAP (Cat. #IT-21)
Neuraxial drug delivery in pain management: An overview of past, present, and future
Yaksh TL, dos Santo G, Lemes J, Malange K (2023) Neuraxial drug delivery in pain management: An overview of past, present, and future. Anaesthesiology doi: 10.1016/j.bpa.2023.04.003
Objective: Activation of neuraxial nociceptive linkages leads to a high level of encoding of the message that is transmitted to the brain and that can initiate a pain state with its attendant emotive covariates. The authors review the encoding of this message and describe the how it is subject to regulation by pharmacological targeting of dorsal root ganglion and dorsal horn systems.
Summary: Authors provide an overview of the past, present and future directions of the biology, pharmacology and technology relevant to the use of the neuraxial route. SP-SAP was used as a neuraxial toxin to eliminate NK1R expressing cells, which characteristic of neurons known to be the second order neurons responding to C fiber input. Delivery of SP-SAP results in long-lasting loss of NK1 bearing dorsal horn neurons and analgesia.
Related Products: SP-SAP (Cat. #IT-07)
Targeting a vulnerable septum-hippocampus cholinergic circuit in a critical time window ameliorates tau-impaired memory consolidation
Wu D, Yu N, Gao Y, Xiong R, Liu L, Lei H, Jin S, Liu J, Liu Y, Xie J, Liu E, Zhou Q, Liu Y, Li S, Wei L, Lv J, Yu H, Zeng W, Zhou Q, Xu F, Luo MH, Zhang Y, Yang Y, Wang JZ (2023) Targeting a vulnerable septum-hippocampus cholinergic circuit in a critical time window ameliorates tau-impaired memory consolidation. Mol Neurodegener 18(1):23. doi: 10.1186/s13024-023-00614-7 PMID: 37060096
Objective: There is an urgent need to study the targeting strategy for the MS-hippocampus cholinergic pathway to rescue tau-impaired memory.
Summary: Abnormal tau accumulation and cholinergic degeneration are hallmark pathologies in the brains of patients with Alzheimer’s disease (AD). However, the sensitivity of cholinergic neurons to AD-like tau accumulation and strategies to ameliorate tau-disrupted spatial memory in terms of neural circuits still remain elusive. The authors found that cholinergic neurons with an asymmetric discharge characteristic in the MS-hippocampal CA1 pathway are vulnerable to tau accumulation. Photoactivating MS-CA1 cholinergic inputs within a critical 3 h time window during memory consolidation efficiently improved tau-induced spatial memory deficits in a theta rhythm dependent manner. 192-IgG-Saporin was used to create an Alzheimer’s Disease animal model.
Related Products: 192-IgG-SAP (Cat. #IT-01)
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Non-image-forming functional roles of OPN3, OPN4 and OPN5 photopigments
Karthikeyan R, Davies WIL, Gunhaga L (2023) Non-image-forming functional roles of OPN3, OPN4 and OPN5 photopigments. J Photochem Photobiol 15:100177. doi: 10.1016/j.jpap.2023.100177
Objective: To review recent studies that focus on the non-image-forming functional roles of the OPN3, OPN4, and OPN5 photopigments.
Summary: This publication explores the non-image-forming functions of OPN3, OPN4, and OPN5 photopigments, highlighting their roles in various physiological processes such as regulation of circadian rhythms, pupillary light responses, modulation of sleep, mood, and hormone secretion, providing insights into the diverse functions of these photopigments beyond vision.
Related Products: Melanopsin-SAP (Cat. #IT-44)
KNDy neurons as the GnRH pulse generator: Recent studies in ruminants
Nestor CC, Merkley CM, Lehman MN, Hileman SM, Goodman RL (2023) KNDy neurons as the GnRH pulse generator: Recent studies in ruminants. Peptides 164:171005. doi: 10.1016/j.peptides.2023.171005 PMID: 36990389
Objective: This publication aims to summarize and provide an overview of recent studies investigating the role of KNDy neurons as the pulse generator for gonadotropin-releasing hormone (GnRH) release in ruminants.
Summary: Recent studies in ruminants, specifically sheep and cows, have investigated the role of KNDy neurons in driving the pulsatile release of GnRH. These studies have demonstrated the rhythmic electrical activity of KNDy neurons, coinciding with the pulsatile secretion of GnRH in ewes, suggesting their central role as the pulse generator. Additionally, the expression patterns of genes related to KNDy neurons and GnRH pulsatility have been examined in cows, revealing variations throughout the estrous cycle and indicating a potential involvement of KNDy neurons in regulating GnRH release in this species. These findings contribute to our understanding of reproductive physiology in ruminants and have implications for both animal and human reproductive health.
Related Products: NKB-SAP (Cat. #IT-63)
Locus coeruleus-noradrenergic modulation of trigeminal pain: Implications for trigeminal neuralgia and psychiatric comorbidities
Donertas-Ayaz B, Caudle RM (2023) Locus coeruleus-noradrenergic modulation of trigeminal pain: Implications for trigeminal neuralgia and psychiatric comorbidities. Neurobiol Pain 13:100124. doi: 10.1016/j.ynpai.2023.100124 PMID: 36974102
Objective: To summarize the knowledge about the involvement of noradrenaline in acute and chronic trigeminal pain conditions and how the activity of the locus coeruleus (LC) noradrenergic neurons changes in response to acute and chronic pain conditions and how these changes might be involved in pain-related comorbidities including anxiety, depression, and sleep disturbance.
Summary: LC inhibition of nociceptive transmission in acute pain and in longterm neuropathic pain increases the tonic activity of LC-NA neurons. These changes may contribute to impaired descending pain modulation and pain-related comorbidities such as depression, anxiety, and sleep disorders.
Usage: Elimination of NA neurons via injection of anti-dopamine β-hydroxylase-saporin (Anti-DBH-SAP) into the lateral ventricle and trigeminal brainstem nuclei three weeks after infraorbital nerve injury attenuated mechanical allodynia
Related Products: Anti-DBH-SAP (Cat. #IT-03)
Acute and chronic lipopolysaccharide-induced stress changes expression of proinflammatory cytokine genes in the rat brain region-specifically and affects learning and memory.
Zaichenko MI, Philenko P, Sidorina V, Grigoryan GA (2023) Acute and chronic lipopolysaccharide-induced stress changes expression of proinflammatory cytokine genes in the rat brain region-specifically and affects learning and memory. Biochemistry Moscow 88:526-538. doi: 10.1134/S0006297923040089
Objective: Goal of the work was to conduct comparative analysis of the effects of acute and chronic lipopolysaccharide- induced stress on the behavior of rats in the Morris water maze test and on expression of mRNA of proinflammatory cytokines and BDNF in different brain structures.
Summary: Chronic stress, depression, and other neuropsychiatric disorders have been often associated with inflammation processes and activity of the brain immune system. In order to investigate association of neuroinflammation with such disorders the model of proinflammatory bacterial lipopolysaccharide intoxication was used. In the experiments with rats, acute lipopolysaccharide (LPS)-induced stress improved learning in the Morris water maze and caused substantial increase of the TNF-α and IL-1β mRNA concentrations in the hippocampus and amygdala, but not in the frontal lobe in comparison with the control animals. Hprt and Ywhaz genes were selected for use as molecular biology reference genes based on the analysis of the rat hippocampus transcriptome from the work done by Dobryakova, Y.V. et. al (2018) Intracerebroventricular administration of 192IgG-saporin alters expression of microglia-associated genes in the dorsal but not ventral hippocampus.
Related Products: 192-IgG-SAP (Cat. #IT-01)
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Targeting nociceptive and cholinergic nerves in irradiated oropharyngeal cancer model reveals novel mechanism for dysphagia
Myers B, Islam S, Gleber Netto FO, Debnath KC, Srivastava S, Xie T, Akhter S, Adebayo AA, Miller J, Lothumalia S, Sathiskumar HN, Amit M (2024) Targeting nociceptive and cholinergic nerves in irradiated oropharyngeal cancer model reveals novel mechanism for dysphagia. Cancer Neuroscience Symposium
Objective: Explore the hypothesis that modulation of cholinergic (CHAT+) and nociceptive (CGRP+) neurons correlate with improved dysphagia.
Summary: Oropharyngeal squamous cell carcinoma is one of the most common types of head and neck cancer. Treatment for OPSCC includes surgery, radiation therapy, chemotherapy, or a combination of therapies. Despite advances in treatment, dysphagia (difficulty swallowing) is still a major burden for patients with OPSCC. The study established a novel murine OPSCC model to explore the role of nerves in dysphagia with cholinergic (CHAT) and nociceptive (CGRP) neurons playing an important role in swallowing outcomes. Targeting CHAT and CGRP could be a novel strategy for OPSCC patients with dysphagia.
Usage: 500 ng of Anti-ChAT-SAP was injected into the trigeminal ganglion in mice.
Related Products: Anti-ChAT-SAP (Cat. #IT-42)