Effects of Exercise on Behavioral Rhythms and Mental Health in Mice with Circadian Rhythm Disorders

Masahiro Wakayama, Hideki Moriyama, Hanlin Jiang, Chunxiao He, Junpei Hatakeyama
Purpose:

This study aimed to investigate whether exercise improves behavioral rhythm and mental health in a mouse model of circadian rhythm disorder, while also examining changes in clock gene expression in brain regions.


Methods:

Forty-eight C57BL/6J male mice were randomly divided into following four groups: control group (C), circadian rhythm disorder group (CD), circadian rhythm disorder followed by aerobic exercise group (CD+AE), and circadian rhythm disorder followed by resistance exercise group (CD+RE) . Circadian rhythm disruption was induced by reversing the light-dark cycle of the mice every three days. Aerobic exercise involved treadmill running at 12m/min, and resistance exercise consisted of climbing 30% body weight. Both were performed daily at ZT12 for 4 weeks. Behavioral rhythms were measured during the final week of the intervention, and anxiety-and depression-like behaviors were assessed using behavioral tests. After the intervention, the prefrontal cortex of mice was sampled at ZT0 (the beginning of the light phase) and ZT12 (the beginning of the dark phase) to analyze mRNA expression changes of the clock genes Bmal1, Per2, and Rev-erbα. Statistical analysis was performed using one-way ANOVA with Tukey HSD test for post-hoc multiple comparisons, and significance was set at p 0.05.



Results:

The CD group exhibited disrupted behavioral rhythms and a significant increase in anxiety- and depression-like behaviors compared to the C group (p 0.05). The CD + AE and CD + RE groups exhibited nearly normal behavioral rhythms, similar to the C group, and showed a significant reduction in anxiety- and depression-like behaviors compared to the CD group (p 0.05). The expression levels of all genes were significantly different at both time points in the C group (p 0.05), but not in the CD group. Bmal1 mRNA expression levels in the CD + AE and CD + RE groups were similar to those in the C group, whereas the expression levels of Per2 and Rev-erbα genes showed no significant difference between the two time points.

Conclusion(s):

Our findings revealed that exercise can mitigate mental health issues resulting from circadian rhythm disruption and help sustain normal Bmal1 gene expression in the prefrontal cortex.

Implications:

This study offers evidence to support the development of exercise programs for future mental health treatments and also establishes a foundation for addressing human mental health challenges.

Funding acknowledgements:
This work was supported by Japan Society for the Promotion of Science KAKENHI Grant Numbers 23H03246 and 23K27936.
Keywords:
Exercise
Circadian rhythm
Mental health
Primary topic:
Mental health
Second topic:
Health promotion and wellbeing/healthy ageing/physical activity
Third topic:
Basic science including molecular and cellular health
Did this work require ethics approval?:
Yes
Name the institution and ethics committee that approved your work:
Kobe University and was approved by the Animal Experimentation Committee.
Provide the ethics approval number:
approval number: P221211
Has any of this material been/due to be published or presented at another national or international conference prior to the World Physiotherapy Congress 2025?:
No

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