Wheel‐Running Exercise Alleviates Anxiety‐Like Behavior via Down‐Regulating S‐Nitrosylation of Gephyrin in the Basolateral Amygdala of Male Rats

Author:

Yang Ping‐Fen12,Nie Tai‐Lei12,Sun Xia‐Nan12,Xu Lan‐Xin12,Ma Cong3,Wang Fang124,Long Li‐Hong124,Chen Jian‐Guo124ORCID

Affiliation:

1. State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases Department of Pharmacology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China

2. The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province Wuhan 430030 China

3. Key Laboratory of Molecular Biophysics of the Ministry of Education College of Life Science and Technology Huazhong University of Science and Technology Wuhan 430030 China

4. Hubei Shizhen Laboratory Wuhan 430030 China

Abstract

AbstractPhysical exercise has beneficial effect on anxiety disorders, but the underlying molecular mechanism remains largely unknown. Here, it is demonstrated that physical exercise can downregulate the S‐nitrosylation of gephyrin (SNO‐gephyrin) in the basolateral amygdala (BLA) to exert anxiolytic effects. It is found that the level of SNO‐gephyrin is significantly increased in the BLA of high‐anxiety rats and a downregulation of SNO‐gephyrin at cysteines 212 and 284 produced anxiolytic effect. Mechanistically, inhibition of SNO‐gephyrin by either Cys212 or Cys284 mutations increased the surface expression of GABAAR γ2 and the subsequent GABAergic neurotransmission, exerting anxiolytic effect in male rats. On the other side, overexpression of neuronal nitric oxide synthase in the BLA abolished the anxiolytic‐like effects of physical exercise. This study reveals a key role of downregulating SNO‐gephyrin in the anxiolytic effects of physical exercise, providing a new explanation for protein post‐translational modifications in the brain after exercise.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

Publisher

Wiley

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