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Myelin in adult brains undergoes dynamic remodeling through oligodendrocyte precursor cells (OPCs) differentiation into oligodendrocytes (OLs) and the degeneration of pre\u2010existing myelin. However, how chronic stress alters myelin dynamics and whether this represents a therapeutic target remains unclear. Here, adult mice subjected to 4\u2010h daily restraint for 2\u2009weeks exhibited significant anxiety, depression, and social deficits. Histological examinations revealed reduced OPC and OL density, decreased c\u2010Fos\u2010positive neurons, and loss of synaptic proteins in the brains exposed to chronic stress. To understand the dynamic changes of myelin, cell\u2010lineage labeling and tracing demonstrated that chronic stress exposure remarkably inhibited oligodendrogenesis in the medial prefrontal cortex (mPFC), motor cortex, hippocampus, and amygdala, as revealed by the NG2\n                    <jats:sup>CreERT<\/jats:sup>\n                    ; Tau\u2010mGFP line, but did not significantly change pre\u2010existing myelin as revealed by a newly generated line for mature OLs and myelin. To explore the role of myelinogenesis changes, adult myelin formation was inhibited by Olig2 conditional knockout in OPCs, resulting in decreased neuronal synaptic proteins and activity, accompanied by anxiety and depressive\u2010like behaviors. Conversely, enhancing myelinogenesis through conditional deletion of the M1R in OPCs of stressed mice resulted in higher number of c\u2010Fos\u2010positive neurons, elevated synaptic protein expression, and a partial reversal of the behavioral deficits. Importantly, treating the stressed animal with the pro\u2010myelination drug clemastine phenocopied the effects of M1R deletion on histological and behavioral disorders. Together, our findings demonstrate that enhancing oligodendrogenesis represents a promising strategy to rescue CRS\u2010caused behavioral disorders.\n                  <\/jats:p>","DOI":"10.1002\/glia.70217","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T11:29:36Z","timestamp":1786447776000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhancing Oligodendrogenesis Rescues Chronic Stress\u2010Induced Behavioral Disorders Involving Neuronal and Synaptic Reorganization"],"prefix":"10.1002","volume":"74","author":[{"given":"Yu\u2010Peng","family":"Dai","sequence":"first","affiliation":[{"name":"Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Department of Histology and Embryology Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Can\u2010Ling","family":"Xu","sequence":"additional","affiliation":[{"name":"Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Department of Histology and Embryology Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Luo","sequence":"additional","affiliation":[{"name":"Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Department of Histology and Embryology Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0931-9696","authenticated-orcid":false,"given":"Zhi\u2010Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Department of Histology and Embryology Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo\u2010Xiao","family":"Meng","sequence":"additional","affiliation":[{"name":"Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Department of Histology and Embryology Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Lin","family":"Li","sequence":"additional","affiliation":[{"name":"Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Department of Histology and Embryology Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An\u2010Cheng","family":"Yu","sequence":"additional","affiliation":[{"name":"Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Department of Histology and Embryology Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Department of Histology and Embryology Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing","family":"Gao","sequence":"additional","affiliation":[{"name":"Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Department of Histology and Embryology Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Department of Histology and Embryology Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Department of Histology and Embryology Third Military Medical University (Army Medical University)  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1956-0553","authenticated-orcid":false,"given":"Tao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Histology and Embryology &amp; K.K. 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