{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:05:16Z","timestamp":1787162716880,"version":"build-2736575974"},"reference-count":68,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,12,11]],"date-time":"2022-12-11T00:00:00Z","timestamp":1670716800000},"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":["no. 31771220"],"award-info":[{"award-number":["no. 31771220"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Early life stress alters brain\u2010derived neurotrophic factor (BDNF) promoter IV methylation and BDNF expression, which is closely related to the pathophysiological process of depression. However, the role of abnormal methylation of BDNF induced by stress during adolescence due to depression has not yet been clarified. In this study, adolescent mice were exposed to chronic unpredictable mild stress (CUMS). Depression\u2010like behaviors, BDNF promoter IV methylation, expression of DNA methyltransferases (DNMTs), demethylation machinery enzymes, BDNF protein levels, and neuronal development in the prefrontal cortex (PFC) and hippocampus (HIP) were assessed in adolescent and adult mice. The DNMT inhibitor, 5\u2010Aza\u20102\u2010deoxycytidine (5\u2010AzaD), was used as an intervention. Stress in adolescence induces behavioral dysfunction, elevated methylation levels of BDNF promoter IV, changes in the expression of DNMT, and demethylation machinery enzymes in adolescent and adult mice. Additionally, the stress in adolescence induced lower levels of BDNF and abnormal hippocampal doublecortin (DCX) expression in adolescent and adult mice. However, DNMT inhibitor treatment in adolescent\u2010stressed mice relieved the abnormal behaviors, normalized the methylation level of BDNF promoter IV, BDNF protein expression, expression of DNMTs, and demethylation machinery enzymes, and improved the neuronal development of adult mice. These results suggest that stress in adolescence induces short\u2010 and long\u2010term hypermethylation of BDNF promoter IV, which is regulated by DNMTs, and leads to the development of depression.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc15735-fig-0007-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.15735","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T07:47:09Z","timestamp":1669880829000},"page":"624-642","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Involvement of brain\u2010derived 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