Study of the enteric nervous system in the distal colon in an animal model of Alzheimer's disease

• Grant number: 24/11158-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2024
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Patricia Castelucci
• Grantee: Leticia Cipriano Albino
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The brain-gut axis is a bidirectional pathway of communication between the central and enteric nervous systems, so that disorders in the brain or gastrointestinal tract do not remain restricted to the site of origin. Several studies are based on the influence of the intestinal microbiota on neurodegenerative diseases. It is believed that, in situations of dysbiosis, bacterial metabolites may end up crossing the intestinal epithelium, traveling through the innervations of the enteric nervous system and reaching the central nervous system via the vagus nerve, where they stimulate immune cells and unbalance the neural environment. In Alzheimer's disease, a neurodegenerative pathology with a high incidence mainly among the elderly population, there is a huge disturbance in neuronal physiology due to the formation of senile plaques and fibrillar tangles which, in turn, intensify the action of microglia, leading to greater production of molecules pro-inflammatory stimulators of neurodestructive processes. In this sense, there is the possibility that part of the cytokines and, mainly altered proteins produced in Alzheimer's disease may travel down the brain-gut axis and reach the gastrointestinal tract, destabilizing the intestinal environment and, consequently, the neurons of the enteric nervous system and their glial cells.In turn, it is important to add that, due to the bidirectional nature of the axis between systems, pathological processes begin in the ENS and reach the CNS via the ascending vagal route, leading to the development of neurological diseases. In this study, the objective is to analyze the changes in the components of the nervous system present in mice models of Alzheimer's disease and also to compare the results obtained with those observed in the distal colon of mice treated with the anti-neuroinflammatory compound AD16, in order to understanding the scope of action of this drug.