Effects of Voluntary Running Wheel Exercise-Induced Extracellular Vesicles on Anxiety

Anxiety disorders are the most frequently diagnosed psychological condition, associated with serious comorbidities including excessive fear and interference with daily life. Drugs for anxiety disorders are typically prescribed but the side effects include weight gain, nausea, and sleepiness. Exercis...

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Main Authors: Kyeong Jin Yoon, Suhong Park, Seung Hee Kwak, Hyo Youl Moon
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-07-01
Series:Frontiers in Molecular Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnmol.2021.665800/full
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author Kyeong Jin Yoon
Suhong Park
Seung Hee Kwak
Hyo Youl Moon
Hyo Youl Moon
Hyo Youl Moon
author_facet Kyeong Jin Yoon
Suhong Park
Seung Hee Kwak
Hyo Youl Moon
Hyo Youl Moon
Hyo Youl Moon
author_sort Kyeong Jin Yoon
collection DOAJ
description Anxiety disorders are the most frequently diagnosed psychological condition, associated with serious comorbidities including excessive fear and interference with daily life. Drugs for anxiety disorders are typically prescribed but the side effects include weight gain, nausea, and sleepiness. Exercise is an effective treatment for anxiety. Exercise induces the release of extracellular vesicles (EVs) into the circulation, which transmit signals between organs. However, the effects of exercise-induced EVs on anxiety remain poorly understood. Here, we isolated EVs from the sera of mice that were sedentary or that voluntarily exercised. We characterized the changes in the miRNA profile of serum EVs after 4 weeks of voluntary exercise. miRNA sequencing showed that 82 miRNAs (46 of which were positive and 36 negative regulators) changed after exercise. We selected genes affected by at least two miRNAs. Of these, 27.27% were associated with neurotrophin signaling (9.09% with each of central nervous system neuronal development, cerebral cortical cell migration, and peripheral neuronal development). We also analyzed behavioral changes in mice with 3 weeks of restraint stress-induced anxiety after injection of 20 μg amounts of EVs from exercised or sedentary mice into the left cerebral ventricle. We found that exercise-derived EVs reduced anxiety (compared to a control group) in a nest-building test but found no between-group differences in the rotarod or open field tests. Exercise-derived EVs enhanced the expression of neuroactive ligand-receptor interaction genes. Thus, exercise-derived EVs may exhibit anti-anxiety effects and may be of therapeutic utility.
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spelling doaj.art-6b62fb480d734d0a8694bbc91652b7df2022-12-21T20:13:46ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992021-07-011410.3389/fnmol.2021.665800665800Effects of Voluntary Running Wheel Exercise-Induced Extracellular Vesicles on AnxietyKyeong Jin Yoon0Suhong Park1Seung Hee Kwak2Hyo Youl Moon3Hyo Youl Moon4Hyo Youl Moon5Department of Physical Education, Seoul National University, Seoul, South KoreaDepartment of Physical Education, Seoul National University, Seoul, South KoreaDepartment of Physical Education, Seoul National University, Seoul, South KoreaDepartment of Physical Education, Seoul National University, Seoul, South KoreaInstitute of Sport Science, Seoul National University, Seoul, South KoreaInstitute on Aging, Seoul National University, Seoul, South KoreaAnxiety disorders are the most frequently diagnosed psychological condition, associated with serious comorbidities including excessive fear and interference with daily life. Drugs for anxiety disorders are typically prescribed but the side effects include weight gain, nausea, and sleepiness. Exercise is an effective treatment for anxiety. Exercise induces the release of extracellular vesicles (EVs) into the circulation, which transmit signals between organs. However, the effects of exercise-induced EVs on anxiety remain poorly understood. Here, we isolated EVs from the sera of mice that were sedentary or that voluntarily exercised. We characterized the changes in the miRNA profile of serum EVs after 4 weeks of voluntary exercise. miRNA sequencing showed that 82 miRNAs (46 of which were positive and 36 negative regulators) changed after exercise. We selected genes affected by at least two miRNAs. Of these, 27.27% were associated with neurotrophin signaling (9.09% with each of central nervous system neuronal development, cerebral cortical cell migration, and peripheral neuronal development). We also analyzed behavioral changes in mice with 3 weeks of restraint stress-induced anxiety after injection of 20 μg amounts of EVs from exercised or sedentary mice into the left cerebral ventricle. We found that exercise-derived EVs reduced anxiety (compared to a control group) in a nest-building test but found no between-group differences in the rotarod or open field tests. Exercise-derived EVs enhanced the expression of neuroactive ligand-receptor interaction genes. Thus, exercise-derived EVs may exhibit anti-anxiety effects and may be of therapeutic utility.https://www.frontiersin.org/articles/10.3389/fnmol.2021.665800/fullexerciseextracellular vesicleanxietymiRNAICV injection
spellingShingle Kyeong Jin Yoon
Suhong Park
Seung Hee Kwak
Hyo Youl Moon
Hyo Youl Moon
Hyo Youl Moon
Effects of Voluntary Running Wheel Exercise-Induced Extracellular Vesicles on Anxiety
Frontiers in Molecular Neuroscience
exercise
extracellular vesicle
anxiety
miRNA
ICV injection
title Effects of Voluntary Running Wheel Exercise-Induced Extracellular Vesicles on Anxiety
title_full Effects of Voluntary Running Wheel Exercise-Induced Extracellular Vesicles on Anxiety
title_fullStr Effects of Voluntary Running Wheel Exercise-Induced Extracellular Vesicles on Anxiety
title_full_unstemmed Effects of Voluntary Running Wheel Exercise-Induced Extracellular Vesicles on Anxiety
title_short Effects of Voluntary Running Wheel Exercise-Induced Extracellular Vesicles on Anxiety
title_sort effects of voluntary running wheel exercise induced extracellular vesicles on anxiety
topic exercise
extracellular vesicle
anxiety
miRNA
ICV injection
url https://www.frontiersin.org/articles/10.3389/fnmol.2021.665800/full
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