Cellular and Molecular Neurobiology

Author: Marcela Adriana Brocco | Email: mbrocco@iib.unsam.edu.ar

Giuliana Torchiana , Catalina Logan , Silvia C. Billi , Marcela A. Brocco , Melisa C. Monteleone

1° Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín (UNSAM)– CONICET
2° Escuela de Bio y Nanotecnologías (EByN-UNSAM)

Mental disorders affect one billion people worldwide. One of their causal agents is chronic stress, which produces a glucocorticoid hypersecretion that can cause mood changes. The serum of stressed individuals contains proteins related to mental diseases, several of them transported by extracellular vesicles (EVs). Among them, M6a, a stress-sensitive neuronal protein whose expression is reduced in the hippocampus of stressed animals. Our aim was to study whether modulating M6a levels in EVs and their administration can alleviate some of the stressed-induced deleterious effects. Since large amounts of EVs are required, to obtain them without using large animal cohorts, we isolated EVs from the hippocampal cell line HT22. To modulate M6a levels we used two strategies: culture treatment with the synthetic glucocorticoid dexamethasone (DEX) or EVs loaded with a plasmid encoding M6a (M6a-EVs). Both treatments increased the M6a cellular levels with respect to the control. Also, after 24 h of intranasal M6a-EVs administration in naive (non-stressed) mice improved their performance in the forced swimming test. Since animals exposed to chronic stress exhibit changes similar to those reported in human depressed patients, we will evaluate whether administration of VEs-M6a to animals exposed to chronic stress can alleviate some of the consequences of stress. Thus, in vitro obtained EVs loaded with molecules of interest could be used as a novel treatment for stress-induced disorders.