Abstract
To observe the effects of refined Xiaoyaosan (XYS) on the depressive-like behaviors in rats with chronic unpredictable mild stress (CUMS), and to explore the relationship between the changes of neurosteroids and mRNA expressions of their synthesis and metabolic enzymes, and the mechanism of XYS in the treatment of depression. Methods: Eighty-four healthy male Sprague-Dawley rats were randomly divided into normal group, model group, XYS group and fluoxetine group. The latter three groups were subjected to 21 days of CUMS to prepare the stress depression model. Rats in the XYS group, and fluoxetine group were given intragastric administration with refined XYS and fluoxetine, respectively. The behavioral changes of the rats were observed after 21 days. The contents of pregnenolone (PREG), progesterone (PROG) and alloprognanolone (ALLO) in the plasma of rats were measured by ELISA. The levels of PREG, PROG and ALLO in the hippocampus and amygdala tissues were measured by LC-MS/MS. The mRNA expressions of 3α-hydroxysteroid dehydrogenase (3α-HSD), 3β-hydroxysteroid dehydrogenase (3β-HSD), cholesterol side-chain cleavage enzyme (P450scc) and 5α-reductase (5a-R) in the hippocampus and amygdala were detected by RT-qPCR methods. Results: There were changes in the model rats. The contents of PREG, PROG and ALLO changed similarly, which reflected in the decrease of PROG and ALLO, and the increase of PREG. The mRNA expression of P450scc was increased, and the mRNA expressions of 3α-HSD, 3β-HSD and 5a-R were decreased. Refined XYS could improve the behaviors of rats and the biological indicators. Conclusions: There is a neurosteroid dysfunction in the brain region of depression rat model animals, and the mechanism of refined XYS depression treatment may be related to the regulation of the control of mRNA expression of related synthesis and metabolic enzymes in the hippocampus and amygdala, further affecting the contents of neurosteroids.
Highlights
Depression is a common emotional disorder disease, in which patients have no interest in anything, persistent mood depression, and associated symptoms such as anxiety, physical discomfort, loss of appetite, slow response, and suicidal thoughts [1,2]
There is a neurosteroid dysfunction in the brain region of depression rat model animals, and the mechanism of refined XYS depression treatment may be related to the regulation of the control of mRNA expression of related synthesis and metabolic enzymes in the hippocampus and amygdala, further affecting the contents of neurosteroids
Compared with the model group, the body weights of the normal group, XYS group and fluoxetine group were significantly increased on the 21st day (NN p < 0.01)
Summary
Depression is a common emotional disorder disease, in which patients have no interest in anything, persistent mood depression, and associated symptoms such as anxiety, physical discomfort, loss of appetite, slow response, and suicidal thoughts [1,2]. The hypothesis that depression is due to a decrease of monoamine neurotransmitter is the most prevalent theory, but the drugs targeting the regulation of monoamine neurotransmitter can only alleviate symptoms of some patients [4], indicating that is a decrease of monoamine neurotransmitter is not the only pathogenesis of depression, and the plasticity disorder of the related neural circuity plays a key role [5]. The two are the important components of the emotional center, and the key sites of depression caused by the uncontrolled HPA axis negative feedback and over-activation induced by chronic stress [6,7]. Recent studies have shown that there are abnormal changes of morphology and chemical composition in the limbic system of patients with depression [8,9]
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