Optogenetic stimulation of the brainstem dorsal motor nucleus ameliorates acute pancreatitis

Inflammation 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...

Full description

Saved in:
Bibliographic Details
Published in:Frontiers in immunology 2023-04, Vol.14, p.1166212
Main Authors: Thompson, Dane A, Tsaava, Tea, Rishi, Arvind, Nadella, Sandeep, Mishra, Lopa, Tuveson, David A, Pavlov, Valentin A, Brines, Michael, Tracey, Kevin J, Chavan, Sangeeta S
Format: Article
Language:English
Subjects:
Acute Disease
acute pancreatitis
Brain Stem
cholinergic anti-inflammatory pathway (CAP)
cytokines
dorsal motor nucleus
Humans
Immunology
Inflammation
Optogenetics
Pancreatitis - drug therapy
vagus nerve
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Inflammation 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. Here, 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. Stimulation 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. These 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.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2023.1166212