{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T11:20:58Z","timestamp":1764156058390,"version":"3.46.0"},"reference-count":71,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The cAMP response element\u2010binding protein (CREB) and\n                    <jats:italic>Period1<\/jats:italic>\n                    (\n                    <jats:italic>Per1<\/jats:italic>\n                    ) have been implicated in depression, but their interactive mechanisms remain unclear. This study\u00a0investigated the integrative role of CREB and\n                    <jats:italic>Per1<\/jats:italic>\n                    in depression and explores a potential strategy for rapid antidepressant treatment. Using a chronic unpredictable stress (CUS) model, we conducted behavioral assessments including the sucrose preference test, forced swimming test, elevated plus maze, and open field test. Gene expression was manipulated via stereotaxic surgery and RNA interference (RNAi), while protein levels and viral injection sites were verified through Western blot analysis and immunofluorescence. Additionally, we generated\n                    <jats:italic>Per1<\/jats:italic>\n                    CRE knockout rats using CRISPR\/Cas9, with genotypes confirmed by Sanger sequencing. CUS significantly reduced phosphorylated CREB (pCREB) and PER1 levels in the CA1 region. Both\n                    <jats:italic>Per1<\/jats:italic>\n                    knockdown in CA1 and CRE sequence knockout induced depression\u2010like behaviors, whereas\n                    <jats:italic>Per2<\/jats:italic>\n                    knockdown in CA1 produced mania\u2010like behaviors. Notably, CRE knockout in the\n                    <jats:italic>Per1<\/jats:italic>\n                    promoter increased pCREB binding to the\n                    <jats:italic>Per2<\/jats:italic>\n                    promoter, upregulating PER2 expression in the CA1 and resulting in depression\u2010like phenotypes that are partially lithium\u2010responsive. Treatment with the adenosine A\n                    <jats:sub>1<\/jats:sub>\n                    receptor agonist 2\u2010chloro\u2010N6\u2010cyclopentyladenosine (CCPA) elevated pCREB and PER1 levels in the CA1 and elicited rapid antidepressant effects. These effects were present in heterozygotes but absent in homozygotes with a mutated\n                    <jats:italic>Per1<\/jats:italic>\n                    CRE sequence. These results revealed the pivotal role of the pCREB\u2010CRE\u2010\n                    <jats:italic>Per1<\/jats:italic>\n                    pathway in CUS\u2010induced depression and its mediation of rapid antidepressant\u2010like effects via adenosine A\n                    <jats:sub>1<\/jats:sub>\n                    receptor activation. Moreover, the CRE sequence in the\n                    <jats:italic>Per1<\/jats:italic>\n                    promoter may be a critical molecular link to the pathophysiology of bipolar depression.\n                  <\/jats:p>","DOI":"10.1111\/jpi.70095","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T11:04:12Z","timestamp":1761908652000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Key Role of the CRE Sequence in the\n                    <i>Per1<\/i>\n                    Promoter in Mediating the Switch Between Unipolar and Bipolar Depression\u2010Like Behaviors"],"prefix":"10.1111","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2445-2947","authenticated-orcid":false,"given":"Xin\u2010Ling","family":"Wang","sequence":"first","affiliation":[{"name":"National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence Research Peking University Beijing China"},{"name":"Savaid Medical School University of Chinese Academy of Sciences Beijing China"},{"name":"Department of Psychiatry and Psychotherapy, Medical Center \u2010 University of Freiburg, Faculty of Medicine University of Freiburg Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Tan","sequence":"additional","affiliation":[{"name":"National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence Research Peking University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Wang","sequence":"additional","affiliation":[{"name":"National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence Research Peking University Beijing 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Han","sequence":"additional","affiliation":[{"name":"National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence Research Peking University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan\u2010Xue","family":"Xue","sequence":"additional","affiliation":[{"name":"National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence Research Peking University Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi\u2010Qiu","family":"Meng","sequence":"additional","affiliation":[{"name":"National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence Research Peking University Beijing 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