Gut-to-brain vagal afferences stimulation and its effects on the stress-induced depressive-like symptoms in mice

• Grant number: 19/24631-6
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): January 28, 2022
• Effective date (End): January 27, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Carolina Demarchi Munhoz
• Grantee: Leonardo Santana Novaes
• Supervisor: Ivan Eid Tavares de Araujo
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Research place: Icahn School of Medicine at Mount Sinai, United States
• Associated to the scholarship: 18/19599-3 - The role of glucocorticoids and the vagus nerve afferences on the neuronal activity and plasticity of central circuits and their implications for stress-induced anxiety in rats, BP.PD

Abstract

The bidirectional communication between the gastrointestinal tract (GI) and the brain has gained attention as a therapeutic target for psychiatric disorders, such as depression, anxiety, and stress-related disorders. The vagus nerve is a critical component of the autonomic nervous system implicated in the gut-to-brain communication. Subcutaneously vagal stimulation has been increasingly used as an alternative treatment of resistant depression. Although promising, the therapeutical potential of this approach is not yet clear, nor the biological mechanisms underlying its effects. In a recent study, Dr. de Araujo´s group has shown that there is a vagal gut-to-brain axis pathway to the central reward neurons. Considering that the lack of motivation in depressed patients may be due to a disruption in the proper functioning of the reward system, understanding how vagal afferences influence this phenomenon is of great value in unraveling the mechanisms by which symptoms of depression are established, as well as in contributing to the development of an alternative therapeutic approach to the conventional pharmacological treatments. Preliminarily, in collaboration with Professor De Araújo, we found that the stimulation of vagal afferences from the upper gut partially remitted the social avoidance behavior in the chronically socially defeated mice. Given these promising data, our goal is to identify the origin of the vagal afferences in the GI implicated in the behavioral changes in the socially defeated mice and the potential therapeutic effects of stimulating these pathways in these animals. (AU)