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048 | An alternative model to study stress signals carried by extracellular vesicles

Cellular and Molecular Neurobiology

Author: Giuliana Torchiana | email: torchianagiuliana@gmail.com


Giuliana Torchiana , Catalina Logan , Silvia 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)

Chronic stress produces glucocorticoid hypersecretion that can cause cognition and mood alterations. Notably, stressed individual serum contains proteins linked to stress and neuropsychiatric diseases. Many of such proteins are carried by extracellular vesicles (EVs). Among them, we have identified M6a, a stress-responsive neuronal protein. Now we aim to further study “stressed derived” EVs to find new molecules that could mediate the stress response. First, to ascertain EVs biodistribution, we stained EVs with the DiR dye and administered them intranasally into mice. The stain was observed in the brain and other organs indicating that EVs can reach different tissues. To study the effect of stressed EVs in animal behavior and gene expression high EV amounts are needed. To obtain them avoiding the use of large animal cohorts, we isolated EVs from hippocampal neurons and from the hippocampal cell line HT22 treated with the synthetic glucocorticoid dexamethasone (DEX). As a measure of DEX effects, M6a levels in cells and EVs were analyzed. We found that DEX increased cellular M6a levels compared to control in both neurons and HT22 cells. DEX also increased M6a levels in EVs. Effects of DEX-EVs administration in mice will be explored. Our results suggest that DEX might induce differential loading of molecules on EVs. Thus we present here an in vitro source of EVs loaded with stress molecules to be used as an alternative tool to investigate stress signal molecules and effects.

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