targeted-toxins

Jin H, Li M, Jeong E, Castro-Martinez F, Zuker CS (2024) A body–brain circuit that regulates body inflammatory responses. Nature 630(8017):695-703. doi: 10.1038/s41586-024-07469-y PMID: 38692285

Objective: To show that a peripheral immune insult strongly activates the body–brain axis to regulate immune responses.

Summary: Using Anti-DBH-SAP, the authors demonstrate that pro-inflammatory and anti-inflammatory cytokines communicate with distinct populations of vagal neurons to inform the brain of an emerging inflammatory response. In turn, the brain tightly modulates the course of the peripheral immune response. Genetic silencing of this body–brain circuit produced unregulated and out-of-control inflammatory responses. By contrast activating this circuit affords neural control of immune responses.

Usage: Bilateral injection into the caudal nucleus of the solitary tract of mice with Anti-DBH–SAP (IT-03, 20 ng per side).

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Barioni NO, Beduschi RS, da Silva AV, Martins MG, Almeida-Francia CCD, Rodrigues SA, López DE, Gómez-Nieto R, Horta-Júnior JAC (2024) The role of the ventral nucleus of the trapezoid body in the auditory prepulse inhibition of the acoustic startle reflex. Hearing Research 450:109070. doi: 10.1016/j.heares.2024.109070 PMID: 38972084

Objective: To study the acoustic startle response through elimination of the ventral nucleus of the trapezoid body neurons via Anti-ChAT-SAP injection.

Summary: The elimination of ventral nucleus of the trapezoid body (VNTB) is used while measuring the auditory prepulse inhibition and acoustic startle response with and without this group of neurons to study their role in rats. It was found The VNTB stands as the sole identified source of cholinergic inputs to Cochlear root neurons.

Usage: Lesions in the VNTB were performed via a bilateral microinjection of a neurotoxin selective for cholinergic neurons, the anti-ChAT-saporin (IT-42, 0.25 ug/μl, 400 nL)

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

Collins HM, Greenfield S (2024) Rodent models of alzheimer’s disease: Past misconceptions and future prospects. Int J Mol Sci 25(11):6222. doi: 10.3390/ijms25116222 PMID: 38892408

Objective: To outline the various apparent causes of Alzheimer’s Disease (AD) and evaluate the success or otherwise of their reproduction in rodents.

Summary: To understand the pathogenesis of AD and how it progresses through the brain, the authors describe the need of an animal model that reproduces the causal mechanism driving the disease. For decades, researchers have attempted to model AD by recapitulating downstream markers of its pathology, including cholinergic neuron loss, Aβ and tau aggregation, and neuroinflammation. Insights gained from the study of Parkinson’s Disease (PD) show that we must model the actual neurodegenerative mechanisms of AD in adult, wildtype animals by specifically targeting the neural populations first affected by a disease. The authors propose an alternative model, based on the aberrant accumulation of the novel peptide T14. In the review, specific cholinergic neuron degeneration was produced by 192 IgG-saporin, which resulted in degeneration of cholinergic cell bodies and terminals via apoptotic cell death.

See Also:

• Book AA et al. 192 IgG-saporin: I. Specific lethality for cholinergic neurons in the basal forebrain of the rat. J Neuropathol Exp Neurol 53:95-102, 1994.
• McGaughy J et al. The role of cortical cholinergic afferent projections in cognition: impact of new selective immunotoxins. Behav Brain Res 115:251-263, 2000.
• Holley LA et al. Cortical cholinergic deafferentation following the intracortical infusion of 192-IgG-saporin: a quantitative histochemical study. Brain Res 663:277-286, 1994.

Nishioka M, Hata T (2024) Cholinergic interneurons in the dorsal striatum play an important role in the acquisition of duration memory. Eur J Neurosci 59(11):3061-3073. doi: 10.1111/ejn.16337 PMID: 38576223

Objective: To investigate duration-memory formation in the dorsal striatum.

Summary: Rats were sufficiently trained using a peak-interval 20s procedure and then infused with anti-choline acetyltransferase–saporin into the dorsal striatum to cause selective ablation of cholinergic interneurons. Lesions of the cholinergic cells show delayed memory acquisition and suggest dorsal striatum neurons play a role in new duration memory.

Usage: Each group of rats received aCSF or anti-choline acetyltransferase (ChAT)–saporin (Anti-ChAT-SAP, IT-42) at 0.5 μg/μL at 0.5 μl/min for 2 mins.

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

Nirogi R, Jayarajan P, Benade V, Abraham R, Goyal VK (2024) Hits and misses with animal models of narcolepsy and the implications for drug discovery. Expert Opin Drug Discov 19(6):755-768. doi: 10.1080/17460441.2024.2354293 PMID: 38747534

Objective: To review the usage of Orexin-B-SAP treated rats in the development of drug candidates for the treatment of narcolepsy.

Summary: Examines pharmacological agents used for the modeling of narcolepsy in animals and contrasts it with narcolepsy expression in real patients. Additionally summarizes the discovery of the orexin system in narcolepsy and how animal models aided in that discovery.

Usage: Orexin- B-saporin (IT-20) was injected into the lateral hypothalamus of rats.

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

Nodal FR, Leach ND, Keating P, Dahmen JC, Zhao D, King AJ, Bajo VM (2024) Neural processing in the primary auditory cortex following cholinergic lesions of the basal forebrain in ferrets. Hear Res 447:109025. doi: 10.1016/j.heares.2024.109025 PMID: 38733712

Objective: To explore whether behavioral deficits are associated with changes in the response properties of cortical neurons, neural activity was recorded in the primary auditory cortex (A1) of anesthetized ferrets in which cholinergic inputs had been reduced

Summary: Results show that while ACh is required for behavioral adaptation to altered spatial cues, it is not required for maintenance of the spectral and spatial response properties of A1

Usage: Bilateral injections of the immunotoxin ME20.4-SAP in the nucleus basalis (NB)

Related Products: ME20.4-SAP (Cat. #IT-15)

Loften A (2024) Cholinergic modulation of dopamine-related effects of ethanol in the rat. Univ Gothenburg Thesis.

Objective: To explore the role of acetylcholine and cholinergic interneurons (CIN) in ethanol-induced dopamine (DA) release and in the reinforcing effects of ethanol.

Summary: The author’s thesis supports an important role of accumbal CIN in ethanol ́s DA releasing and reinforcing effects, opening up for new potential pharmacological targetsfor treatments of alcohol use disorder.

Usage: in vivo rat model with depletion of accumbal CIN was developed utilizing anti-choline acetyltransferase-saporin (IT-42)

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

Keilholz A, Osman K, Smith C, Streeter K, Ozden I, Lever T, Nichols N (2024) Tongue exercise-induced plasticity in upper airway EMG activity in a model of hypoglossal motor neuron loss. Am Physiol Summit 39(S1) doi: 10.1152/physiol.2024.39.S1.1405

Objective: To study the impact of XII LMN degeneration and develop therapies to improve swallowing and breathing function/coordination.

Summary: The authors developed a novel rodent model of XII LMN loss using intralingual injections of CTB-SAP. Tongue exercise appears to enhance XII axis plasticity to improve upper airway function and coordination.

Usage: Intralingual injection of CTB-SAP (IT-14)

Related Products: CTB-SAP (Cat. #IT-14)

Lewis R, Smith C, Nichols N (2024) Spinal TNF-α receptor expression in a rodent model of respiratory motor neuron death. Am Physiol Summit 39(S1) doi: 10.1152/physiol.2024.39.S1.1401

Objective: To create a model from respiratory deficit and study the role of inflammation in phrenic long-term facilitation.

Summary: Some neurodegenerative diseases are characterized by deficits in respiratory neurons, which can be modeled in rodents through the ablation of C4 TNFR1 expressing neurons. Phrenic long-term facilitation induced by acute intermittent hypoxia is observed in the model and at different times following the ablation to elucidate mechanisms of plasticity at different points of breathing deficits.

Usage: Intrapleural injection of CTB-SAP (25 ug, IT-14) in rats.

Related Products: CTB-SAP (Cat. #IT-14)

Toledo C, Del Rio R (2024) Cardiorespiratory disturbances in Alzheimer’s disease: A focus on the contribution of sympathetic premotor neurons. Am Physiol Summit 39(S1) doi: 10.1152/physiol.2024.39.S1.2540

Objective: To characterize cardiorespiratory function in AD patients and then to determine the role of RVLM-C1 neurons in autonomic and sleep-disordered breathing in APP/PS1 double transgenic mice, and experimental model showing AD-like pathology.

Summary: Results show that RVLM-C1 neurons play a main role in the development/maintenance of cardiorespiratory disorders in experimental AD.

Usage: Bilateral stereotaxic injections of Anti-DBH-SAP (IT-03) into the RVLM were used to selectively destroy C1 neurons.

Related Products: Anti-DBH-SAP (Cat. #IT-03)