targeted-toxins

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)

Ren X, Liu S, Virlogeux A, Kang SJ, Brusch J, Liu Y, Dymecki SM, Han S, Goulding M, Acton D (2023) Identification of an essential spinoparabrachial pathway for mechanical itch. Neuron 30:S0896-6273. doi: 10.1016/j.neuron.2023.03.013 PMID: 37023756

Objective: Study pathways of mechanical and chemical itch.

Summary: Mechanical and chemical itch are controlled by separate pathways within the body. Gpr83ligand PEN peptide conjugated to saporin (PEN-SAP) was used to selectively ablate CAlcrl projection neurons, alleviating mechanical itch sensitivity in wild-type mice. Substance-P saporin (SSP-SAP) was injected into mice and used as a negative control for the ablation of itch-sensitive neurons in the areas targeted. The ablated mice maintained mechanical itch sensitivity.

Usage: Intrathecal injections of SSP-SAP (IT-11; 100 ng/10 ml 0.9% sterile saline), biotinylated Gpr83 ligand (PEN) conjugated to Strepavidin-ZAP (IT-27), PEN-SAP, 3 ug/10 ml, 0.9% sterile saline, or control Blank-SAP (IT-21) in mice.

Related Products: SSP-SAP (Cat. #IT-11), Streptavidin-ZAP (Cat. #IT-27), Blank-SAP (Cat. #IT-21)

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 PMID: 37080938

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.

Chan YY, Ho PY, Swartzrock L, Rayburn M, Nofal R, Thongthip S, Weinberg KI, Czechowicz A (2023) Non-genotoxic restoration of the hematolymphoid system in fanconi anemia. Transplant Cell Ther 29(3):164.e1-164.e9. doi: 10.1016/j.jtct.2022.08.015 PMID: 35995393

Objective: Evaluate the efficacy of different CD117 mAb agents and immunosuppression on hematopoietic stem cell (HSC) depletion, and their ability to safely establish therapeutic donor hematopoiesis post-HSCT in Fancomi Anemia (FA) disease models.

Summary: Patients with FA are particularly sensitive to genotoxic agents in the treatment of blood and immune diseases. By targeting the disease through use of a CD117 antibody conjugate to an antagonist agent, some of the sensitivities of Fancomi anemia can be circumvented compared to traditional therapeutics. The results demonstrated the efficacy of several different non-genotoxic monoclonal antibody-based conditioning strategies in Fancomi anemia.

Usage: Biotinylated CD117 mAb mixed with Streptavidin-ZAP (Anti-CD117-SAP) and was administered on Day 0. Anti-CD117-SAP was diluted with sterile PBS and administered at 1.5 mg/kg via i.v. injection.

Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD117-SAP (Cat. #IT-83)

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)

Hankerd K, Koo H, McDonough KE, Wang J, Pariyar R, Tang SJ, Chung JM, La JH (2023) Gonadal hormone-dependent nociceptor sensitization maintains nociplastic pain state in female mice. Pain 164(2):402-412. doi: 10.1097/j.pain.0000000000002715

Objective: To determine whether gonadal hormones are necessary for the development and maintenance of a peripherally maintained nociplastic pain state in female mice.

Summary: Ovariectomized females still developed a nociplastic pain state, but it was not maintained by peripheral afferent activity or spinal microglia. The findings indicate that gonadal hormones are essential for sustaining this pain state by promoting persistent sensitization of AITC-responsive afferents.

Usage: Mac-1-SAP (IT-06) or unconjugated saporin (PR-01) was administered intrathecally at 8.85 µM in 5 µL to evaluate the role of spinal microglia in nociplastic pain maintenance.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)

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)

McDonough KE, Hammond R, Wang J, Tierney J, Hankerd K, Chung JM, La JH (2023) Spinal GABAergic disinhibition allows microglial activation mediating the development of nociplastic pain in male mice. Brain Behav Immun 107:215-224. doi: 10.1016/j.bbi.2022.10.013 PMID: 36273650

Objective: To investigate whether spinal microglia drive the transition from acute injury-induced pain to nociplastic pain in males, and if so, how they are activated by normally innocuous stimulation after peripheral injury.

Summary: The results demonstrate that in males, the transition from acute injury-induced pain to nociplastic pain is driven by spinal microglia causing neuroinflammation and that peripheral injury-induced spinal GABAergic disinhibition is pivotal for normally innocuous stimulation to activate spinal microglia.

Usage: Investigating the mechanisms of transition from acute to nociplastic pain, mice received a single intrathecal injection of unconjugated saporin (PR-01) or Mac-1-saporin (IT-06, 8.85 μM, 5 μL)

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06), Saporin (Cat. #PR-01)