Possible participation of circulating extracellular vesicles in depressive-like behavior of Flinders Sensitive Line rats

• Grant number: 22/10187-0
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date until: December 01, 2022
• End date until: May 31, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Sabrina Francesca de Souza Lisboa
• Grantee: Sávio Lima Bastos
• Supervisor: Gregers Wegener
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Aarhus University, Denmark
• Associated to the scholarship: 21/05406-1 - Study of possible changes in the endocannabinoid, endovaniloid, and neuroimmune systems in brain after stimulation of microglia cells: involvement of epigenetic mechanisms, BP.MS

Abstract

Extracellular vesicles (EVs) are important elements in intercellular communication, carrying a variety of molecules, like enzymes, receptors, mRNA, miRNA, and DNA. Microglia cells, the immune cells of the central nervous system (CNS), actively release EVs as messengers in response to inflammatory signals, inducing pro or anti-inflammatory responses in recipient cells. Microglia activation and EVs release are correlated processes, and are also related with neurodegenerative and neuropsychiatric disease, as Parkinson and Alzheimer diseases, and major depressive disorder (MDD). The EVs are able to pass through the brain blood barrier and circulate in blood, making it a suitable peripheral biomarker related to the CNS condition. In MDD, some inflammatory markers are found in the blood of patients, such as cytokines and miRNAs, and are also found in preclinical models of depression. The EVs, besides the utility as biomarkers, can also participate in pathophysiology of diseases as a tool for communication between central nervous system and periphery. Indeed, the transference of extracellular vesicles from body fluids or cell culture media to the blood of animals is able to induce deep changes in behavior and biochemical markers on CNS. Thus, we aim to investigate the effect of EVs from flinders sensitive line (FSL) rats, a genetic model of depression, on the flinder resistant line (FRL), the control animals for FSL. We hypothesize that the transfer of EVs induce a depressive-like behavior in FRL in a similar manner as FSL. Besides that, we will also characterize the mRNA profile of plasma EVs on both lines. (AU)