Treadmill training impacts the skeletal muscle molecular clock after ischemia stroke in rats

Mai Li; Yong Yin; Dongdong Qin

doi:10.1016/j.heliyon.2024.e27430

Treadmill training impacts the skeletal muscle molecular clock after ischemia stroke in rats

Heliyon. 2024 Mar 12;10(6):e27430. doi: 10.1016/j.heliyon.2024.e27430. eCollection 2024 Mar 30.

Authors

Mai Li¹, Yong Yin², Dongdong Qin³

Affiliations

¹ Department of Rehabilitation Medicine, The Second Affiliated Hospital of Kunming Medical University, No. 374, Fengning Street, Dianmian Road, 650101, Kunming, China.
² Department of Rehabilitation Medicine, The Affiliated Hospital of Yunnan University, No. 176, Qingnian Road, 650021, Kunming, China.
³ School of Basic Medical Sciences, Yunnan University of Chinese Medicine, No. 1076 Yuhua Road, Chenggong District, 650500, Kunming, China.

Abstract

Objective: Stroke is frequently associated with muscle mass loss. Treadmill training is considered the most effective treatment for sarcopenia. Circadian rhythms are closely related to exercise and have been extensively studied. The skeletal muscle has its molecular clock genes. Exercise may regulate skeletal muscle clock genes. This study evaluated the effects of early treadmill training on the skeletal muscle molecular clock machinery in rats with stroke and determined the relationship of these changes with exercise-induced improvements in skeletal muscle health.

Materials and methods: Overall, 168 Sprague-Dawley rats were included in this study. We established an ischemic stroke rat model of sarcopenia. Finally, 144 rats were randomly allocated to four groups (36 per group): normal, sham, middle cerebral artery occlusion, and training. Neurological scores, rotating rod test, body weight, muscle circumference, wet weight, and hematoxylin-eosin staining were assessed. Twenty-four rats were used for transcriptome sequencing. Gene and protein expressions of skeletal muscles, such as brain muscle arnt-like 1, period 1, and period 2, were measured by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assays.

Results: Neurological function scores and rotating rod test results improved after treadmill training. Nine differentially expressed genes were identified by comparing the sham group with the hemiplegic side of the model group. Seventeen differentially expressed genes were identified between the hemiplegic and non-hemiplegic sides. BMAL1, PER1, and PER2 mRNA levels increased on both sides after treadmill training. BMAL1 expression increased, and PER1 expression decreased on both sides, whereas PER2 expression decreased on the hemiplegic side but increased on the non-hemiplegic side.

Conclusion: Treadmill training can mitigate muscle loss and regulate skeletal muscle clock gene expression following ischemic stroke. Exercise affects the hemiplegic side and has a positive regulatory effect on the non-hemiplegic side.

Keywords: Circadian rhythm; Ischemia stroke; Sarcopenia; Skeletal muscle molecular clock; Treadmill training.