targeted-toxins

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)

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)

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)

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)

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)

See Also:

• Dornan WA et al. Comparison of site-specific injections into the basal forebrain on water maze and radial arm maze performance in the male rat after immunolesioning with 192 IgG saporin. Behav Brain Res 82:93-101, 1996.

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)

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)

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)

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)

See Also:

• Dobryakova YV et al. Intracerebroventricular administration of 192IgG-saporin alters expression of microglia-associated genes in the dorsal but not ventral hippocampus. Front Mol Neurosci 10:429, 2018.

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 (2023) 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)