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This study was designed to determine whether OG could improve the depressive\u2010like symptoms of perimenopausal depression (PMD) and the possible mechanisms involved. This research was performed on a PMD mice model established by a two\u2010steps method of ovariectomy (OVX) followed CUMS. OG treatment effectively improved the depressive\u2010like behaviors of OVX\u2010CUMS mice, as indicated by increased sucrose intake in sucrose preference test (SPT), reduced immobility time in forced swimming test (FST), and tail suspension test (TST), lower frequency of grooming and defecation, increased actions of rearing, and prolonged duration in the center in open field test (OFT). OG treatment alleviated the OVX\u2010CUMS induced dysfunction of hypothalamic\u2013pituitary\u2010ovarian (HPO) axis by increased serum estradiol (E2) and decreased ovarian hormones follicle stimulating hormone (FSH), luteinizing hormone (LH), and gonadotropin\u2010releasing hormone (GnRH) in serum. Meanwhile, OG reversed the hyperactivity of hypothalamic\u2013pituitary\u2013adrenal (HPA) axis as evidenced by decreased CORT and ACTH in serum, reduced as well as the mRNA and protein expression of corticotropin\u2010releasing hormone (CRH) in hypothalamus and hippocampus. Moreover, OG up\u2010regulated the protein expression of BDNF, TrkB, and phosphorylation level of CREB and ERK1\/2 in hippocampus. These findings demonstrated that OG improves depressive behaviors of OVX\u2010CUMS mice by modulating of HPO\/HPA axis dysfunction, and activating BDNF\u2013TrkB\u2010CREB signaling pathway.<\/jats:p>","DOI":"10.1002\/ptr.7237","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T06:14:17Z","timestamp":1628748857000},"page":"5795-5807","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Orcinol glucoside improves the depressive\u2010like behaviors of perimenopausal depression mice through modulating activity of hypothalamic\u2013pituitary\u2013adrenal\/ovary axis and activating <scp>BDNF<\/scp>\u2010 <scp>TrkB\u2010CREB<\/scp> signaling pathway"],"prefix":"10.1002","volume":"35","author":[{"given":"Junlong","family":"Li","sequence":"first","affiliation":[{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy Anhui Medical University  Hefei 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