Quercetin alleviates chronic unpredictable mild stress‐induced depression‐like behavior by inhibiting NMDAR1 with α2δ‐1 in rats

• DOI: 10.1111/cns.14724
• Publication Date: 2024-04-14T21:08:31Z
• Authors: Mingyan Wang; Xin Wei; Yugai Jia; Chaonan Wang; Xinliu Wang; Xin Zhang; Depei Li; Yuanyuan Wang; Yonggang Gao
• Keywords: Tail suspension test; Stressor; Depression; Chronic Stress

Abstract Background Depression is a serious mental disorder and the most prevalent cause of disability suicide worldwide. Chronic unpredictable mild stress (CUMS) can lead to significant acceleration depression development. Quercetin (Que) flavonoid compound with wide range pharmacological effects. Recent studies have shown that quercetin improve CUMS‐induced depression‐like behavior, but mechanism its improvement still unclear. α2δ‐1 regulatory subunit voltage‐gated calcium channel, which interact N‐methyl‐D‐aspartate receptor (NMDAR) form complex. Objective In this study, we found Que could inhibit increase NMDAR expression in rat hypothalamus induced by CUMS. pain, chronic hypertension other interacts complex, subsequently affects level NMDAR. Consequently, present study aimed investigate antidepressant effect vivo vitro explore action terms interaction between Methods Rats were randomly exposed two stressors every day for 4 weeks establish CUMS model, then sucrose preference test (SPT), forced swimming (FST), tail suspension (TST), open field (OFT) performed detect behavior rats, so as evaluate whether model was successfully established on rats. Experimental techniques such serum enzyme‐linked immunosorbent assay (ELISA), immunofluorescence, Western blot, co‐immunoprecipitation, well experiments, used mechanisms exerts Results Behavioral ELISA results showed produce reduction excitability hypothalamic–pituitary–adrenal (HPA) axis rats improvements their depressive behavior. co‐immunoprecipitation experiments produced decrease NMDAR1 levels interfered binding. addition, neural regulation PC12 cells knocked out gene further verified. Cellular demonstrated led reversal up‐regulation corticosterone‐injured cells, while had no effects knockout. Conclusions has good significantly caused It inhibiting α2δ‐1, interfering NMDAR, reducing HPA axis.