Xiaoyaosan Exerts Antidepressant-Like Effect by Regulating Autophagy Involves the Expression of GLUT4 in the Mice Hypothalamic Neurons.
Xiaoyaosan Exerts Antidepressant-Like Effect by Regulating Autophagy Involves the Expression of GLUT4 in the Mice Hypothalamic Neurons.
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逍遥散通过调节小鼠下丘脑神经元自噬发挥抗抑郁样作用涉及GLUT4的表达
DOI：
10.3389/fphar.2022.873646
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发表时间：
2022
影响因子：
5.6
通讯作者：
Chen, Jia-Xu
中科院分区：
文献类型：
--
作者：
Yang, Fu-Rong;Zhu, Xiao-Xu;Kong, Ming-Wang;Zou, Xiao-Juan;Ma, Qing-Yu;Li, Xiao-Juan;Chen, Jia-Xu
许多研究证明，自噬在抑郁症的发展中起关键作用，并且还影响下丘脑中GLUT4的表达。小米已被证明会以多种方式发挥抗抑郁作用，但其基本机制在下丘脑中调节自噬和glut4的基本机制仍不清楚。因此，在这项研究中，我们建立了一种由慢性不可预测的轻度应激（CUMS）引起的抑郁症的小鼠模型，并建立了自噬阻滞，作为对照的控制，以探索小红亚亚人是否通过影响自噬来施加抗抑郁作用。我们研究了小亚如何对开放田测试，尾悬浮测试和蔗糖偏好测试表现出的行为的影响，以及下丘脑神经元自噬的变化以及GLUT4的变化以及Cums诱导的抑郁小鼠模型中葡萄糖代谢的相关指标。我们发现，Cums和3-MA诱导的小鼠表现出抑郁样的行为变化，LC3表达降低和p62表达增加，表明小鼠下丘脑的自噬水平降低。 GLUT4的表达也降低了，它与通过RAB8和RAB10的自噬水平密切相关。然而，在小火干预后，上述变化有效地逆转了。这些结果表明，小米可以调节下丘脑神经元的自噬和抑郁小鼠中GLUT4的表达。
Many studies have proven that autophagy plays a pivotal role in the development of depression and it also affects the expression of GLUT4 in the hypothalamus. Xiaoyaosan has been shown to exert antidepressant effects in a variety of ways, but its underlying mechanism by which Xiaoyaosan regulates autophagy as well as GLUT4 in the hypothalamus remains unclear. Thus, in this study, we established a mouse model of depression induced by chronic unpredictable mild stress (CUMS), and set up autophagy blockade as a control to explore whether Xiaoyaosan exerts antidepressant effect by affecting autophagy. We examined the effects of Xiaoyaosan on behaviors exhibited during the open field test, tail suspension test and sucrose preference test, and the changes in autophagy in hypothalamic neurons as well as changes in GLUT4 and the related indicators of glucose metabolism in CUMS-induced depressive mouse model. We found that CUMS- and 3-MA-induced mice exhibited depressive-like behavioral changes, with decreased LC3 expression and increased p62 expression, suggesting decreased levels of autophagy in the mouse hypothalamus. The expression of GLUT4 was also decreased, and it was closely related to the level of autophagy through Rab8 and Rab10. Nevertheless, after the intervention of Xiaoyaosan, the above changes were effectively reversed. These results show that Xiaoyaosan can regulate the autophagy in hypothalamic neurons and the expression of GLUT4 in depressed mice.
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