Optogenetic stimulation of the brainstem dorsal motor nucleus ameliorates acute pancreatitis

Frontiers in Immunology

Immunology

David A. Tuveson¹  Sandeep Nadella¹  Arvind Rishi²  Tea Tsaava³  Michael Brines³  Lopa Mishra⁴  Dane A. Thompson⁵  Valentin A. Pavlov⁶  Kevin J. Tracey⁶  Sangeeta S. Chavan⁶ 

[1] Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, United States;Department of Pathology and Laboratory Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, United States;Laboratory of Biomedical Sciences, Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United States;Laboratory of Biomedical Sciences, Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United States;Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hofstra University, Hempstead, NY, United States;Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, United States;Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, NY, United States;Laboratory of Biomedical Sciences, Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United States;The Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, United States;Department of Surgery, Northshore University Hospital, Northwell Health, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United States;Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hofstra University, Hempstead, NY, United States;Laboratory of Biomedical Sciences, Institute for Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United States;The Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, United States;Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hofstra University, Hempstead, NY, United States;

关键词: acute pancreatitis;    dorsal motor nucleus;    vagus nerve;    inflammation;    cytokines;    cholinergic anti-inflammatory pathway (CAP);   

DOI  :  10.3389/fimmu.2023.1166212

 received in 2023-02-14, accepted in 2023-03-28,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionInflammation is an inherently self-amplifying process, resulting in progressive tissue damage when unresolved. A brake on this positive feedback system is provided by the nervous system which has evolved to detect inflammatory signals and respond by activating anti-inflammatory processes, including the cholinergic anti-inflammatory pathway mediated by the vagus nerve. Acute pancreatitis, a common and serious condition without effective therapy, develops when acinar cell injury activates intrapancreatic inflammation. Prior study has shown that electrical stimulation of the carotid sheath, which contains the vagus nerve, boosts the endogenous anti-inflammatory response and ameliorates acute pancreatitis, but it remains unknown whether these anti-inflammatory signals originate in the brain.MethodsHere, we used optogenetics to selectively activate efferent vagus nerve fibers originating in the brainstem dorsal motor nucleus of the vagus (DMN) and evaluated the effects on caerulein-induced pancreatitis.ResultsStimulation of the cholinergic neurons in the DMN significantly attenuates the severity of pancreatitis as indicated by reduced serum amylase, pancreatic cytokines, tissue damage, and edema. Either vagotomy or silencing cholinergic nicotinic receptor signaling by pre-administration of the antagonist mecamylamine abolishes the beneficial effects.DiscussionThese results provide the first evidence that efferent vagus cholinergic neurons residing in the brainstem DMN can inhibit pancreatic inflammation and implicate the cholinergic anti-inflammatory pathway as a potential therapeutic target for acute pancreatitis.

【 授权许可】

Unknown   
Copyright © 2023 Thompson, Tsaava, Rishi, Nadella, Mishra, Tuveson, Pavlov, Brines, Tracey and Chavan