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We investigated the impact of chronic stress on miR200\/BMP\/Olig\u20102 signaling and hippocampal myelination. We also compared the effects of chronic administration of amitriptyline and cholecalciferol on chronically stressed hippocampi. Both amitriptyline and cholecalciferol significantly decreased serum cortisol levels, reduced immobility time in the forced swim test, increased the number of crossed squares in open field test, decreased the hippocampal expression of bone morphogenetic protein 4 (BMP4) and its messenger RNA (mRNA) levels, reduced miR200 expression as compared to untreated chronically stressed rats. Also, both drugs amended the hippocampal neuronal damage, enhanced the surviving cell count, and increased the pyramidal layer thickness of Cornu Ammonis subregion 1 (CA1) and granule cell layer of the dentate gyrus. Cholecalciferol was more effective in increasing the area percentage of myelin basic protein (MBP) and Olig\u20102 positive cells count in hippocampi of chronic stress\u2010exposed rats than amitriptyline, thus enhancing myelination. We also found a negative correlation between the expression of BMP4, its mRNA, miR200, and the immunoexpression of MBP and Olig\u20102 proteins. This work underscores the amelioration of the stress\u2010induced behavioral changes, inhibition of miR200\/BMP4 signaling, and enhancement of hippocampal myelination following chronic administration of either amitriptyline or cholecalciferol, though cholecalciferol seemed more effective in brain remyelination.<\/jats:p>","DOI":"10.1002\/cbin.12200","type":"journal-article","created":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T04:08:26Z","timestamp":1718770106000},"page":"1326-1342","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Amitriptyline and cholecalciferol amend hippocampal histological structure and myelination during stress in Wistar rats via regulating miR200\/BMP4\/Olig\u20102 signaling"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9540-8620","authenticated-orcid":false,"given":"Marian Maher Salib","family":"Roushdy","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Medicine Ain Shams University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7839-6728","authenticated-orcid":false,"given":"Jolly M. 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