Sinisan alleviates depression-like behaviors by regulating mitochondrial function and synaptic plasticity in maternal separation rats
Sinisan alleviates depression-like behaviors by regulating mitochondrial function and synaptic plasticity in maternal separation rats
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Sinisan 通过调节母体分离大鼠的线粒体功能和突触可塑性减轻抑郁样行为
DOI：
10.1016/j.phymed.2022.154395
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发表时间：
2022-09-11
期刊：
影响因子：
7.9
通讯作者：
Zhang, Rong
中科院分区：
文献类型：
--
作者：
Deng, Di;Cui, Yongfei;Zhang, Rong
背景资料：四逆散由四味药组成，是抗抑郁方剂的核心，广泛应用于中医临床治疗早期生活应激所致抑郁症。然而，SNS抗抑郁剂的作用及其确切机制尚未阐明。目的：本研究旨在探讨SNS抗抑郁剂调节线粒体功能改善海马突触可塑性的机制。将90只出生后第0天的SD雄性幼鼠随机分为对照组（ddH（2）0）、模型组（ddH（2）0）、氟西汀组（氟西汀5.0 mg/kg）、SNS-L组（SNS 2.5 g/kg）、SNS-M组（SNS 5.0 g/kg）和SNS-H组（SNS 10.0 g/kg），每组15只。分别于PND 1 ~ PND 21、PND 60 ~ PND 90、PND 83 ~ PND 90、PND 83、PND 90透射电镜观察突触结构和线粒体结构。采用免疫组化和western blot检测PSD-95和SYN的表达水平，采用试剂盒检测海马三磷酸腺苷（ATP）含量，采用western bolt检测Mfn 2、Drp 1和Fis 1蛋白的表达水平。SNS能减轻MS大鼠的抑郁样和焦虑样行为，改善突触和线粒体的损伤，减轻海马ATP含量的下降，结论：SNS可通过调节线粒体功能和突触可塑性，降低早期生活应激所致抑郁障碍的风险。靶向线粒体可能是抗抑郁药的一个新的有前景的治疗途径。
Background: Sinisan (SNS) consists of four kinds of herbs, which is the core of antidepressant prescription widely used in traditional Chinese medicine clinic treatment for depression induced by early life stress. However, the role and precise mechanism of SNS antidepressant have not yet been elucidated.Purpose: This study aimed to investigate the mechanism SNS on antidepressant of regulating mitochondrial function to improve hippocampal synaptic plasticity.Methods: 90 Sprague-Dawley (SD) rats male pups on Post-Natal Day (PND) 0 were randomly divided into Control group (ddH(2)0), Model group (ddH(2)0), Fluoxetine group (5.0 mg/kg fluoxetine), and SNS-L group (2.5 g/kg SNS), SNS-M group (5.0 g/kg SNS) and SNS-H group (10.0 g/kg SNS), 15 animals per group. Maternal separation (MS) from PND1 to PND21, drug intervention from PND60 to PND90, and behavior tests including sucrose preference test, open field test and forced swimming test from PND83 to PND90 were performed. Synaptic structure and mitochondrial structure were observed by TEM. The expression levels of PSD-95 and SYN were detected by immunohistochemistry and western blot test, the adenosine triphosphate (ATP) content in the hippocampus was detected by assay kits, and the expression levels of Mfn2, Drp1 and Fis1 protein were detected by western bolt test.Results: SNS can alleviate depression-like and anxiety-like behaviors in MS rats, improve the damage of synapses and mitochondria, reduce the decrease of ATP in hippocampus, and reverse the expression levels of PSD-95, SYN, Mfn2, Drp1, and Fis1 proteins.Conclusion: SNS reduced the risk of early life stress induced depression disorder via regulating mitochondrial function and synaptic plasticity. Targeting mitochondrial may be a novel prospective therapeutic avenue for antidepressant.