Exploration of the mechanism by which icariin modulates hippocampal neurogenesis in a rat model of depression  

作　　者：Ning-Xi Zeng Hui-Zhen Li Han-Zhang Wang Kai-Ge Liu Xia-Yu Gong Wu-Long Luo Can Yan Li-Li Wu 

机构地区：[1]Research Center for Basic Integrative Medicine,Guangzhou University of Chinese Medicine,Guangzhou,Guangdong Province,China

出　　处：《Neural Regeneration Research》2022年第3期632-642,共11页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.81774102 (to LLW)。

摘　　要：Icariin(ICA) has a significant capacity to protect against depression and hippocampal injury,but it cannot effectively cross the bloodbrain barrier and accumulate in the brain.Therefore,the mechanism by which ICA protects against hippocampal injury in depression remains unclear.In this study,we performed proteomics analysis of cerebrospinal fluid to investigate the mechanism by which ICA prevents dysfunctional hippocampal neurogenesis in depression.A rat model of depression was established through exposure to chronic unpredictable mild stress for 6 weeks,after which 120 mg/kg ICA was administered subcutaneously every day.The results showed that ICA alleviated depressive symptoms,learning and memory dysfunction,dysfunctional neurogenesis,and neuronal loss in the dentate gyrus of rats with depression.Neural stem cells from rat embryonic hippocampi were cultured in media containing 20% cerebrospinal fluid from each group of rats and then treated with 100 μM corticosterone.The addition of cerebrospinal fluid from rats treated with ICA largely prevented the corticosterone-mediated inhibition of neuronal proliferation and differentiation.Fifty-two differentially expressed proteins regulated by chronic unpredictable mild stress and ICA were identified through proteomics analysis of cerebrospinal fluid.These proteins were mainly involved in the ribosome,PI3 K-Akt signaling,and interleukin-17 signaling pathways.Parallel reaction monitoring mass spectrometry showed that Rps4 x,Rps12,Rps14,Rps19,Hsp90 b1,and Hsp90 aa1 were up-regulated by chronic unpredictable mild stress and down-regulated by ICA.In contrast,Htr A1 was down-regulated by chronic unpredictable mild stress and up-regulated by ICA.These findings suggest that ICA can prevent depression and dysfunctional hippocampal neurogenesis through regulating the expression of certain proteins found in the cerebrospinal fluid.The study was approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2017.

关 键 词：cerebrospinal fluid chronic unpredictable mild stress DEPRESSION dysfunctional hippocampal neurogenesis HIPPOCAMPUS ICARIIN PROTEOMICS ribosome pathway 

分 类 号：R453[医药卫生—治疗学] R749.05[医药卫生—临床医学]