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Stress-induced brain extracellular vesicles ameliorate anxiety behavior
Yusuke Mizohata1,2, Yusuke Yoshioka3, Minori Koga4
1Department of Physiology, National Defense Medical College, Tokorozawa, Saitama, Japan.
Translational Psychiatry
|November 19, 2025
Summary
Acute stress triggers brain-derived extracellular vesicles (BDEVs) that reduce anxiety. Specific microRNAs within these BDEVs, like miR-199a-3p, show potential for anxiety disorder therapies.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Extracellular vesicles (EVs) are key intercellular communicators, with brain-derived EVs (BDEVs) regulating neurological functions.
- The brain employs stress responses to maintain homeostasis, but BDEV's role in this is unclear.
Purpose of the Study:
- To investigate the role of BDEVs in modulating the acute stress response.
- To identify molecular mechanisms underlying BDEV-mediated stress modulation.
Main Methods:
- Administration of acute stress-induced BDEVs to mice.
- Analysis of anxiety-related behaviors.
- Identification and testing of specific microRNAs (miRNAs) within BDEVs.
Main Results:
- BDEV administration reduced anxiety-like behaviors in mice.
- Three specific miRNAs (miR-199a-3p, miR-99b-3p, miR-140-5p) from BDEVs replicated this anxiolytic effect.
- miR-199a-3p may reduce anxiety by suppressing Mecp2 in neurons.
Conclusions:
- BDEVs play a role in modulating mental activity during acute stress.
- Specific miRNAs within BDEVs are key mediators of these effects.
- This research provides a basis for developing EV- or miRNA-based therapies for anxiety disorders.
