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Exercise‐induced Extracellular Vesicles’ Effect on Stress.
Author(s) -
Yoon Kyeong Jin,
Cho Hae-Sung,
Lee WonSang,
Moon HyoYoul
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.09935
Subject(s) - anxiety , microrna , medicine , depression (economics) , gene , biology , psychiatry , genetics , macroeconomics , economics
Modern society changes faster and more complicated. It causes stress on mentally and physically. Especially stress can increase anxiety. The evidence that anxiety is associated with mental disorder such as depression and suicide is increasing. This phenomenon elevates social burden in public health. Exercise induces releasing extracellular vesicles (EVs) into circulation system that can be signaling molecules between organs. EVs have micro RNAs (miRNA) that regulate genes through inhibiting translation or degrading messenger RNA. Also, previous studies found that EVs can cross the blood‐brain barrier and it may be the role of neurotransmitters. However, the underlying mechanism of EVs on stress is not fully elucidated. To investigate the direct role of exercise‐derived EVs on brain function, we isolated the EVs from serum of sedentary or voluntary exercised mice. Then we analyzed the behavioral changes with chronic unpredictable mild stress (CUMS) induced anxiety mice after administration of total 0.3 ug of exercise or sedentary derived EVs into the left cerebral ventricle. We found that exercise derived EVs reduced the symptom of anxiety in a nest building test compared to control groups while there were no differences in the rotarod test or oft between groups. Furthermore, we observed that exercise‐derived EVs enhanced the neurogenic markers such as NOR1 and PAX6. We further characterized the changes of miRNA profile packaged in serum EVs after 4 weeks of voluntary exercise. miRNA sequencing results showed that 82 miRNAs (46 genes up and 36 genes down) changed by exercise. Using bioinformatics tools, we found that 17 miRNAs were commonly related with response to oxygen level. Among 8353 predicted targeting genes regulated by these 17 miRNAs, we selected 190 genes which were overlapped above 4 miRNAs. 13.04% of 190 genes were related with central nervous system neuron differentiation and TOR signaling, respectively and 8.7% of genes connected with sarcoplasmic reticulum. These results suggest that exercise‐derived EVs may be involved in anti‐anxiety like effect of exercise partially via neurogenesis. We believe our findings can propose the possibility of therapeutic strategy through exercise‐derived EVs in anxiety disorder. Support or Funding Information This work was supported by the National Research Foundation (NRF, 700‐20190019), Korea Mouse Phenotype Center (NRF, 2019M3A9D5A01102794) and Research Resettlement Fund for the new faculty of Seoul National University.Characters of Extracellular vehicles.Injection of EVs in stress treated mice.