Modified Xiaoyaosan (MXYS) Exerts Anti-depressive Effects by Rectifying the Brain Blood Oxygen Level-Dependent fMRI Signals and Improving Hippocampal Neurogenesis in Mice.
Modified Xiaoyaosan (MXYS) Exerts Anti-depressive Effects by Rectifying the Brain Blood Oxygen Level-Dependent fMRI Signals and Improving Hippocampal Neurogenesis in Mice.
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加味逍遥散 (MXYS) 通过纠正脑血氧水平依赖性 fMRI 信号并改善小鼠海马神经发生发挥抗抑郁作用
DOI：
10.3389/fphar.2018.01098
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发表时间：
2018
影响因子：
5.6
通讯作者：
Lv Z
中科院分区：
文献类型：
--
作者：
Gao L;Huang P;Dong Z;Gao T;Huang S;Zhou C;Lai Y;Deng G;Liu B;Wen G;Lv Z
逍遥散及其改良方作为传统的中药复方，已有大量研究表明具有明确的抗抑郁作用，但其作用机制尚不清楚。本实验室的前期工作已经证实，慢性应激诱导的抑郁症可导致脑血氧水平依赖性（BOLD）功能磁共振成像（fMRI）信号紊乱，并伴有海马神经元可塑性受损、脑源性神经营养因子（BDNF）含量降低、齿状回成年神经元数量和复杂性减少等。我们推测，逍遥散的中药配方可以发挥抗抑郁作用，通过恢复这些神经生物学功能障碍和纠正BOLD-fMRI信号。为了验证这一假设，我们研究了改良逍遥散（MXYS）对抑郁样行为的影响，以及海马神经发生和BOLD信号在慢性不可预测的轻度应激（CNOMS）诱导的抑郁症小鼠模型。MXYS对CNS诱导的抑郁症具有与经典抗抑郁药物（盐酸氟西汀）相似的抗抑郁作用，显著减轻抑郁样行为，改善海马神经发生，逆转边缘系统（特别是海马）中BOLD的激活。这些结果表明，MXYS通过纠正小鼠海马中的BOLD信号来减轻CNS诱导的抑郁行为。这些新的结果表明，MXYS具有抗抑郁作用，并伴有改善BOLD信号和海马神经发生，这表明脑区域的BOLD-fMRI信号可能是评价新型抗抑郁药物的关键组成部分。
As the traditional Chinese herbal formula, Xiaoyaosan and its modified formula have been described in many previous studies with definite anti-depressive effects, but its underlying mechanism remains mystery. Previous work in our lab has demonstrated that depression induced by chronic stress could generate brain blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals disorder, accompanied by the impairment of hippocampal neuronal plasticity, decrease of brain-derived neurotrophic factor, and reduction of the number and complexity of adult neurons in the dentate gyrus. We hypothesized that herbal formula based on Xiaoyaosan could exert anti-depressive effects through restoring these neurobiological dysfunctions and rectifying BOLD-fMRI signals. To test this hypothesis, we examined the effect of modified Xiaoyaosan (MXYS) on depressive-like behaviors, as well as hippocampal neurogenesis and BOLD signals in a mice model of chronic unpredictable mild stress (CUMS)-induced depression. MXYS exerted anti-depressant effects on CUMS-induced depression that were similar to the effects of classical antidepressants drug (fluoxetine hydrochloride), with a significant alleviation of depressive-like behaviors, an improvement of hippocampal neurogenesis, and a reversal of activation of BOLD in the limbic system, particularly in the hippocampus. These results suggested that MXYS attenuated CUMS-induced depressive behaviors by rectifying the BOLD signals in the mice hippocampus. These novel results demonstrated that MXYS had anti-depressive effects accompanied by improving BOLD signals and hippocampal neurogenesis, which suggested that BOLD-fMRI signals in brain regions could be a key component for the evaluation of novel antidepressant drugs.
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