Exercise Ameliorates Anxious Behavior and Promotes Neuroprotection Through Osteocalcin in VCD-induced Menopausal Mice

Overview

Journal CNS Neurosci Ther

Specialties Neurology
Pharmacology

Date 2023 Jul 4

PMID 37402694

Authors

Yiting Kang

Jie Yao

Xiaohang Gao

Hao Zhong

Yifei Song

Xiaohui Di

Zeguo Feng

Lin Xie

Jianbao Zhang

Affiliations

Soon will be listed here.

Abstract

Aims: As the ovaries age and women transition to menopause and postmenopause, reduced estradiol levels are associated with anxiety and depression. Exercise contributes to alleviate anxiety and depression and the bone-derived hormone osteocalcin has been reported to be necessary to prevent anxiety-like behaviors. The aim of this study was to investigate the effects of exercise on anxiety behaviors in climacteric mice and whether it was related to osteocalcin.

Methods: Menopausal mouse model was induced by intraperitoneal injection of 4-vinylcyclohexene diepoxide (VCD). Open field, elevated plus maze, and light-dark tests were used to detect anxious behavior in mice. The content of serum osteocalcin was measured and its correlation with anxiety behavior was analyzed. BRDU and NEUN co-localization cells were detected with immunofluorescence. Western blot was applied to obtain apoptosis-related proteins.

Results: The VCD mice showed obvious anxiety-like behaviors and 10 weeks of treadmill exercise significantly ameliorated the anxiety and increased circulating osteocalcin in VCD mice. Exercise increased the number of BRDU and NEUN co-localization cells in hippocampal dentate gyrus, reduced the number of impaired hippocampal neurons, inhibited the expression of BAX, cleaved Caspase3, and cleaved PARP, promoted the expression of BCL-2. Importantly, circulating osteocalcin levels were positively associated with the improvements of anxiety, the number of BRDU and NEUN co-localization cells in hippocampal dentate gyrus and negatively related to impaired hippocampal neurons.

Conclusion: Exercise ameliorates anxiety behavior, promotes hippocampal dentate gyrus neurogenesis, and inhibits hippocampal cell apoptosis in VCD-induced menopausal mice. They are related to circulating osteocalcin, which are increased by exercise.

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Exercise ameliorates anxious behavior and promotes neuroprotection through osteocalcin in VCD-induced menopausal mice.

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