Neural Regeneration Research ›› 2018, Vol. 13 ›› Issue (5): 837-845.doi: 10.4103/1673-5374.232478

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Chaihu-Shugan-San exerts an antidepressive effect by downregulating miR-124 and releasing inhibition of the MAPK14 and Gria3 signaling pathways

Qiong Liu1, Ning-Ning Sun2, Zheng-Zhi Wu2, Da-Hua Fan3, 4, Mei-Qun Cao2   

  1. 1 Department of Cardiovascular Medicine, XiangYa Hospital of Central South University, Changsha, Hunan Province, China
    2 Shenzhen Institute of Geriatrics, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen,Guangdong Province, China
    3 The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, Guangdong Province, China
    4 Chinese and Wsetern Integrative Medicine, Shcool of Medicine, Jinan University, Guangzhou, Guangdong Province, China.
  • Received:2018-04-19 Online:2018-05-15 Published:2018-05-15
  • Contact: Mei-Qun Cao, Ph.D. or Da-Hua Fan, Ph.D.,mqcao111@163.com or fan_dahua@163.com.
  • Supported by:

    This work was supported by the National Natural Science Foundation of China, No. 81503415, 81574038, 81603671; the China Postdoctoral Science Foundation Grant, No. 2016M600709; a grant from the Science and Technology Planning Project of Guangdong Province of China, No. 2014A020221062; a grant from the Science and Technology Planning Project of Shenzhen City of China, No.JCYJ20150401170235349, JCYJ20160428105749954.

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Abstract:

Dysregulation of miR-124 has been reported to be involved in the pathophysiology of depression. Chaihu-Shugan-San, a traditional Chinese medicine, has antidepressive activity; however, the underlying mechanisms remain unclear. In this study, to generate a rodent model of depression, rats were subjected to a combination of solitary confinement and chronic unpredictable mild stress for 28 days. Rats were intragastrically administered Chaihu-Shugan-San (2.835 mL/kg/d) for 4 weeks, once a day. Real-time reverse-transcription quantitative polymerase chain reaction, miRNA microarray, western blot assay and transmission electron microscopy demonstrated that Chaihu-Shugan-San downregulated miR-124 expression and upregulated the mRNA and protein levels of mitogen-activated protein kinase 14 (MAPK14) and glutamate receptor subunit 3 (Gria3). Chaihu-Shugan-San also promoted synapse formation in the hippocampus. The open field test, sucrose consumption test and forced swimming test were used to assess depression-like behavior. After intragastric administration of Chaihu-Shugan-San, sucrose consumption increased, while the depressive behaviors were substantially reduced. Together,these findings suggest that Chaihu-Shugan-San exerts an antidepressant-like effect by downregulating miR-124 expression and by releasing the inhibition of the MAPK14 and Gria3 signaling pathways

Key words: nerve regeneration, traditional Chinese medicine, Chaihu-Shugan-San, depression, open-field test, sucrose consumption test, forced swimming test, miR-124, neural plasticity, MAPK14, Gria3, neural regeneration