Study of the short-chain fatty acid receptor, GPR41, in the enteric neurons of mice submitted to experimental ulcerative colitis

• Grant number: 22/04010-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2022
• Effective date (End): August 09, 2024
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Patricia Castelucci
• Grantee: Jheniffer Rayane de Lima Duarte
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The short-chain fatty acid receptor coupled to the G protein contributes to the maintenance of the intestinal barrier, and protection against pathogens and inflammation. The presence of short-chain fatty acid receptors GPR41 in the enteric nervous system has been observed. Intestinal inflammation affects the enteric nervous system. The literature demonstrates that butyrate has been promising in the treatment of ulcerative colitis due to its anti-inflammatory and neuromodulatory effects. Butyrate is a short-chain fatty acid produced by bacteria in the intestinal microbiota from the fermentation of dietary fibers. Therefore, this project aims to study the GPR41 receptor and analyze the effect of the use of Butyrate on the neurons of the myenteric plexus of mice submitted to experimental ulcerative colitis. For this, 2, 4, 6, trinitrobenzene sulfonic acid (TNBS) will be injected into the large intestine of C57BL/6 animals and the vehicle (alcohol) will be injected in the Sham group. The animals submitted to colitis will be treated with Sodium Butyrate, via gavage, and the Sham group will receive an equivalent volume of saline. The animals will be euthanized 7 and 14 days after TNBS or vehicle injection and Sodium Butyrate treatment. The following will be analyzed: A) The presence of the GPR41 receptor and its colocalization with PGP9.5 immunoreactive neurons (panneuronal); B) GPR41 and PGP9.5 receptor-positive neurons/ganglia and C) PGP9.5 immunoreactive neuron profiles areas. Data will be analyzed by Nikon 80i fluorescence and Confocal Laser Scanning microscopes.(AU)