AI Article Synopsis

  • There is a need for better tools to specifically target vagal afferent neurons (VAN) connected to the gut; researchers use a neurotoxin called CCK-SAP to selectively ablate these neurons in rats and mice.
  • * In vivo experiments show that CCK-SAP effectively reduces the VAN in the upper gastrointestinal tract but spares efferent neurons, thus not affecting certain neural pathways crucial for feeding.
  • * This novel technique enhances the understanding of gut-to-brain signaling effects in various biological contexts while offering greater tissue specificity compared to traditional methods.

Article Abstract

There is a lack of tools that selectively target vagal afferent neurons (VAN) innervating the gut. We use saporin (SAP), a potent neurotoxin, conjugated to the gastronintestinal (GI) hormone cholecystokinin (CCK-SAP) injected into the nodose ganglia (NG) of male Wistar rats to specifically ablate GI-VAN. We report that CCK-SAP ablates a subpopulation of VAN in culture. In vivo, CCK-SAP injection into the NG reduces VAN innervating the mucosal and muscular layers of the stomach and small intestine but not the colon, while leaving vagal efferent neurons intact. CCK-SAP abolishes feeding-induced c-Fos in the NTS, as well as satiation by CCK or glucagon like peptide-1 (GLP-1). CCK-SAP in the NG of mice also abolishes CCK-induced satiation. Therefore, we provide multiple lines of evidence that injection of CCK-SAP in NG is a novel selective vagal deafferentation technique of the upper GI tract that works in multiple vertebrate models. This method provides improved tissue specificity and superior separation of afferent and efferent signaling compared with vagotomy, capsaicin, and subdiaphragmatic deafferentation. We develop a new method that allows targeted lesioning of vagal afferent neurons that innervate the upper GI tract while sparing vagal efferent neurons. This reliable approach provides superior tissue specificity and selectivity for vagal afferent over efferent targeting than traditional approaches. It can be used to address questions about the role of gut to brain signaling in physiological and pathophysiological conditions.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668568PMC
http://dx.doi.org/10.1152/ajpgi.00095.2017DOI Listing

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