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

Abstract

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.

Exercise-Induced Extracellular Vesicles Delay the Progression of Prostate Cancer

“…Although the EV levels were increased in some animals, the mean EV concentration and size were not significantly different in the Pre-RUN and Post-RUN plasma samples. These results are in line with several other studies finding no significant changes in the EV concentration after the exercise ( Lovett et al, 2018 ; Hou et al, 2019 ; Yoon et al, 2021 ). This controversy suggests that different types, intensity and duration of exercise may affect the kinetics of EV release from various cell types or their clearance from the circulation in different ways.…”

Chronic contractile activity induced skeletal muscle-derived extracellular vesicles increase mitochondrial biogenesis in recipient myocytes via transmembrane or peripheral membrane proteins

“…We have previously shown that extracellular particles (EP) isolated following acute contractile activity increased cell count but not viability in myoblasts, but that study was done with a different exercise regimen, isolation method, and treatment protocol [42]. Another study reported that chronic exercise-derived EVs increased cell viability in Neuro2A cells, a mouse neuroblastoma cell line, also using different exercise regimen and protocols [71]. Interestingly, EV-depleted media treatment reduced cell count compared to conditioned media and CCA-EV treated cells, illustrating the EVdependent nature of these adaptations, and in concordance with previous work [42].…”

Urinary extracellular vesicle as a potential biomarker of exercise-induced fatigue in young adult males

“…Since exercise modifies the urinary proteome (Kohler et al 2015 ) and EV miRNA profile in plasma (Yoon et al 2021 ), and both urine and urinary EVs comprise the plasma proteome (Dear et al 2013 ; Harpole et al 2016 ), we hypothesized that exercise could change the urinary EV miRNA contents. After 20 m SRT and 1 h of rest, a total of 9 miRNAs in urinary EVs were found to be altered.…”