{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:56:20Z","timestamp":1791082580660,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T00:00:00Z","timestamp":1665014400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673716"],"award-info":[{"award-number":["81673716"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic traumatic stress results in various psychiatric disorders, especially posttraumatic stress disorder (PTSD). Previous study demonstrated that curculigoside (CUR) a component of <jats:italic>Rhizoma Curculiginis<\/jats:italic> prevented fear extinction and stress\u2010induced depression\u2010like behaviors. However, its effects on PTSD and the mechanisms are still not completely clear. In this study, we observed typical PTSD\u2010like phenotypes, synaptic deficit, and reduction of BDNF\/TrkB signaling pathway in mice receiving modified single prolonged stress and electrical stimulation (SPS&amp;S). By contrast, systemic administration of CUR blocked PTSD\u2010like phenotypes and synaptic deficits, including reduction of BDNF\/TrkB signaling pathway, GluA1 and Arc expression. Importantly, CUR reversed the impairment of PKA signaling pathway elicited by PTSD. We further confirmed that the effects of CUR on synaptic function were through PKA signaling pathway, as H\u201089, an inhibitor of PKA blocked the effect of CUR on behavioral changes and BDNF\/TrkB signaling pathway. Thereafter, we verified that CUR on synaptic function were through PKA pathway using direct intracerebral injection of CUR and H\u201089. Direct intracerebral injection of CUR activated PKA\/CREB\/BDNF\/TrkB, which was blocked by H\u201089. Additionally, the docking results showed high binding energies of CUR with A2AR, AC, PRKACA, and PRKAR1A, which might indicate that CUR functions through regulating PKA signaling pathway. In conclusion, CUR prevented the behavioral changes and hippocampal synaptic deficits elicited by PTSD through activating cAMP\u2010PKA signaling.<\/jats:p>","DOI":"10.1002\/ptr.7658","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T13:21:27Z","timestamp":1665062487000},"page":"759-773","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Curculigoside rescues hippocampal synaptic deficits elicited by <scp>PTSD<\/scp> through activating <scp>cAMP\u2010PKA<\/scp> signaling"],"prefix":"10.1002","volume":"37","author":[{"given":"Manman","family":"Ji","sequence":"first","affiliation":[{"name":"Key Laboratory of Xin'an Medicine, the Ministry of Education and Key Laboratory of Molecular Biology (Brain diseases) Anhui University of Chinese Medicine  Hefei 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