Xiaoyaosan Exerts Antidepressant-Like Effect by Regulating Autophagy Involves the Expression of GLUT4 in the Mice Hypothalamic Neurons

Abstract

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.

Xiaoyaosan ameliorates depressive-like behavior and susceptibility to glucose intolerance in rat: involvement of LepR-STAT3/PI3K pathway in hypothalamic arcuate nucleus

“…Recently, a selective knockout of GLUT4 in the brains of mice showed glucose intolerance, hepatic insulin resistance, and decreased glucose uptake in the brain, suggesting a critical role of brain GLUT4 in whole-body glucose homeostasis [ 45 ]. In the present study, GLUT4 expression was reduced in the ARC, which is consistent with the reduced GLUT4 expression in the hypothalamus of CUMS-induced depressed mice in our previous study [ 46 ]. In fact, extensive research has focused on the role of brain GLUT in stress-induced glucose metabolism disorders, in which GLUT1 and GLUT4 are the main glucose transporters involved in stress affecting systemic glucose homeostasis [ 47 , 48 ].…”

Electroacupuncture Alleviates Depressive-like Behavior by Modulating the Expression of P2X7/NLRP3/IL-1β of Prefrontal Cortex and Liver in Rats Exposed to Chronic Unpredictable Mild Stress

“…Sucrose preference test (SPT) [ 46 ] was performed on 4 consecutive days, and included a two-day sugar water adaptation phase, a one-day water deprivation phase, and a one-day test phase. On the first two days (at 8 a.m.), every rat was once simultaneously introduced to two bottles containing 100 mL of either 1% sucrose solution or tap water.…”

Flavonoids contribute most to discriminating aged Guang Chenpi (Citrus reticulata ‘Chachi’) by spectrum‐effect relationship analysis between LC‐Q‐Orbitrap/MS fingerprint and ameliorating spleen deficiency activity

“…Mice were observed for 6 min, and the activity in the last 4 min was recorded. The immobility time of each mouse was calculated (Yang et al, 2022 ).…”