Dataset Information

Identifying overtraining biomarkers through proteomic analysis of extracellular vesicles derived from the central nervous system of male mice

ABSTRACT: Overtraining, which results in central nervous system (CNS)-fatigue-related symptoms, lead to a long-term decline in performance. This study investigated CNS-derived EV protein content under overtraining conditions to identify potential biomarkers. Eight-week-old C57BL/6J mice were randomly divided into three groups: sedentary (SED, n=7), exercise control (EX, n=8), and overtraining (OT, n=9) groups. The OT underwent an 8-week downhill treadmill-based overtraining induction protocol. Exercise capacity was assessed using the incremental load, exhaustion, grip strength, and rotarod tests, while motor deficits, depression and anxiety were assessed using the nest building test. Proinflammatory cytokines were measured in blood plasm, skeletal muscle, and brain tissue. CNS-derived EVs were isolated using a two-step EV isolation protocol. Isolated EVs underwent proteomic analyses. Mice exhibited a significant decrease in aerobic exercise capacity, high-intensity exercise tolerance, and muscular strength. OT increased quadriceps IL-6 and hypothalamic IL-1β/TNFα compared to EX. Plasma IL-2 levels tended to be higher in OT than in EX. Proteomic analysis of CNS-derived EVs revealed a decrease in lipid metabolism-related proteins. Valosin-containing proteins and catalase, which are upregulated in organs under oxidative stress, were increased. Therefore, CNS-derived EV protein contents indicated CNS fatigue under overtraining conditions.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Blood Plasma

SUBMITTER: Dong Heon Yi

LAB HEAD: Hyo Youl Moon

PROVIDER: PXD069257 | Pride | 2025-11-10

REPOSITORIES: Pride

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Identifying overtraining biomarkers through proteomic analysis of extracellular vesicles derived from the central nervous system of male mice.

Yi Dong Heon DH Hwang Eun Seon ES Ko Kang Eun KE Kim Tae Yeon TY Cho Yun Seo YS Yook Ki Hoon KH da Silva Adelino S R ASR Moon Hyo Youl HY

Physiological reports 20251101 21

Overtraining, which results in central nervous system (CNS)-fatigue-related symptoms, leads to a long-term decline in performance. This study investigated CNS-derived EV protein content under overtraining conditions to identify potential biomarkers. Eight-week-old C57BL/6J mice were randomly divided into three groups: sedentary (SED, n = 7), exercise control (EX, n = 8), and overtraining (OT, n = 9) groups. The OT group underwent an 8-week downhill treadmill-based overtraining induction protocol ...[more]

PMID: 41178061

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Project description:Individuals affected by post-covid condition (PCC) show an increased fatigue and the so-called post-exertion malaise (PEM) that led health professionals to advise against exercise although accumulating evidence indicate the contrary. The goal of this study is to determine the impact of a closely monitored 8-week mixed exercise program on physical capacity, symptoms, fatigue, systemic oxidative stress and plasma proteomic profiles of PCC cases. Methods: Twenty-five women and men with PCC assigned sequentially to exercise (n = 15) and non-exercise (n = 10) groups. Individuals with no PCC served as a control group. The exercise program included cardiovascular and resistance exercises. Physical capacity, physical activity level and the presence of common PCC symptoms were measured before and after the intervention. Fatigue was measured the day following each exercise session. Plasma and PBMC samples were collected at the beginning and end of the training program. Glutathione and deoxyguanosine levels in PBMC and plasma proteomic profiles were evaluated. Results: Bicep Curl (p=0.040) and STS-30 (p=0.043) improved to a greater extent in the exercise group than in the non-exercise group. An interaction effect was also observed for the level of physical activity (p=0.007) with a positive effect of the program on their daily functioning and without any adverse effects on general or post-effort fatigue. Glutathione levels showed marked improvement after exercise. Discernable changes were observed in the plasma proteomics profile with certain proteins involved in inflammatory response (SA100A8) decreasing in the exercise group. Conclusion: Supervised exercise adapted to the level of fatigue and ability is safe and effective in PCC patients in improving their general physical capacity and wellbeing. Systemic molecular markers that accompany physical improvement can be monitored by analyzing plasma proteomics and markers of oxidative stress. Large-scale studies will help identify promising molecular markers to objectively monitor patient improvement.

			Action	DRS
	DHY_EX1.raw	Raw
	DHY_EX2.raw	Raw
	DHY_EX3.raw	Raw
	DHY_OT.msf	Msf
	DHY_OT.pdResult	Other