{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:51:57Z","timestamp":1790859117796,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,4,14]],"date-time":"2024-04-14T00:00:00Z","timestamp":1713052800000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Depression is a serious mental disorder and the most prevalent cause of disability and suicide worldwide. Chronic unpredictable mild stress (CUMS) can lead to a significant acceleration of depression development. Quercetin (Que) is a flavonoid compound with a wide range of pharmacological effects. Recent studies have shown that quercetin can improve CUMS\u2010induced depression\u2010like behavior, but the mechanism of its improvement is still unclear. \u03b12\u03b4\u20101 is a regulatory subunit of voltage\u2010gated calcium channel, which can interact with N\u2010methyl\u2010D\u2010aspartate receptor (NMDAR) to form a complex.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>In this study, we found that Que could inhibit the increase of \u03b12\u03b4\u20101 and NMDAR expression in rat hypothalamus induced by CUMS. In pain, chronic hypertension and other studies have shown that \u03b12\u03b4\u20101 interacts with the NMDAR to form a complex, which subsequently affects the expression level of NMDAR. Consequently, the present study aimed to investigate the antidepressant effect of Que in\u00a0vivo and in\u00a0vitro and to explore its mechanism of action in terms of the interaction between \u03b12\u03b4\u20101 and NMDAR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Rats were randomly exposed to two stressors every day for 4\u2009weeks to establish a CUMS rat model, then sucrose preference test (SPT), forced swimming test (FST), tail suspension test (TST), and open field test (OFT) were performed to detect the behavior of CUMS rats, so as to evaluate whether the CUMS rat model was successfully established and the improvement effect of Que on CUMS\u2010induced depression\u2010like behavior in rats. Experimental techniques such as serum enzyme\u2010linked immunosorbent assay (ELISA), immunofluorescence, Western blot, and co\u2010immunoprecipitation, as well as in\u00a0vitro experiments, were used to investigate the mechanisms by which Que exerts its antidepressant effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Behavioral and ELISA test results showed that Que could produce a reduction in the excitability of the hypothalamic\u2013pituitary\u2013adrenal (HPA) axis in CUMS rats and lead to significant improvements in their depressive behavior. Western blot, immunofluorescence, and co\u2010immunoprecipitation experiments showed that Que produced a decrease in NMDAR1 and \u03b12\u03b4\u20101 expression levels and interfered with \u03b12\u03b4\u20101 and NMDAR1 binding. In addition, the neural regulation mechanism of Que on antidepressant effect in PC12 cells knocked out \u03b12\u03b4\u20101 gene was further verified. Cellular experiments demonstrated that Que led to a reversal of up\u2010regulation of NMDAR1 and \u03b12\u03b4\u20101 expression levels in corticosterone\u2010injured PC12 cells, while Que had no effects on NMDAR1 expression in PC12 cells with the \u03b12\u03b4\u20101 gene knockout.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Que has a good antidepressant effect and can significantly improve the depression\u2010like behavior caused by CUMS. It exerts antidepressant effects by inhibiting the expression level of \u03b12\u03b4\u20101, interfering with the interaction between \u03b12\u03b4\u20101 and NMDAR, and then reducing the excitability of the HPA axis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.14724","type":"journal-article","created":{"date-parts":[[2024,4,14]],"date-time":"2024-04-14T17:08:31Z","timestamp":1713114511000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Quercetin alleviates chronic unpredictable mild stress\u2010induced depression\u2010like behavior by inhibiting NMDAR1 with \u03b12\u03b4\u20101 in rats"],"prefix":"10.1111","volume":"30","author":[{"given":"Mingyan","family":"Wang","sequence":"first","affiliation":[{"name":"College of Integrative Chinese and Western Medicine Hebei University of Chinese Medicine  Shijiazhuang 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