Abstract
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.
Highlights
As a complicated mental and neuropsychological disease, depressive disorder is a serious challenge worldwide (Steel et al, 2014; Greenberg et al, 2015)
Mice exposed to chronic unpredictable mild stress (CUMS) induced hippocampal neural damage and triggered the disorders of blood oxygen leveldependent (BOLD)–functional magnetic resonance imaging (fMRI) signal in the hippocampus, which were reversed by treatments with modified Xiaoyaosan (MXYS)
Our study suggested that the MXYS administration ameliorated depression by improving the hippocampal neurogenesis and rectifying the BOLD–fMRI signals in mice with chronic stress exposure
Summary
As a complicated mental and neuropsychological disease, depressive disorder is a serious challenge worldwide (Steel et al, 2014; Greenberg et al, 2015). Exposure to chronic stress is widely regarded as the significant risk factor for the development of depressive disorder. Studies of patients with depressive disorder have appeared dendritic atrophy in hippocampus and prefrontal cortex, as well as reduction of hippocampal volume (Campbell et al, 2004). Depression induced by stress produces neurobiological alterations, along with decreases in brain-derived neurotrophic factor (BDNF) expression and hippocampal neurons proliferation, survival, and maturation (Lussier et al, 2013). The consequences of depressive disorder include focal changes within certain brain regions, and disturbances of function within them
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