Stress-induced brain extracellular vesicles ameliorate anxiety behaviour.

Extracellular vesicles (EVs), nano particles secreted by all types of cells, serve as a communication network, carrying information through the bloodstream to distant cells1,2. Notably, brain cells secrete EVs that play a crucial role in regulating neurological functions3-5. Meanwhile the brain detects acute stress and activates mechanisms to enhance stress resistance and maintain homeostasis6,7. However, the specific contribution of brain-derived extracellular vesicles (BDEVs) in modulating the stress response remains elusive. Here we found that administration of the acute stress-induced BDEVs to mice reduced anxiety-related behaviours, and this reduction was also induced by the administration of only three microRNAs (miRNAs) (miR-199a-3p, miR-99b-3p and miR-140-5p) included in the acute stress-induced BDEVs. Furthermore, we showed that miR-199a-3p contributes to the mechanism of the anxiolytic effect through the suppression of Mecp2 in neurons. These findings elucidate the role of BDEVs in modulating mental activity under acute stress and provide insights into the underlying molecular mechanisms. Our results open up new avenues for therapeutic strategies in the treatment of anxiety disorders using EVs or miRNAs.