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Studies show it takes 2\u20133\u00a0weeks for the mood\u2010enhancing effects, which indicate other mechanisms may underlie their treatment effects. Here, we investigated the role of white matter in treatment and pathogenesis of depression using an unpredictable chronic mild stress (<jats:styled-content style=\"fixed-case\">UCMS<\/jats:styled-content>) mouse model. Desvenlafaxine (<jats:styled-content style=\"fixed-case\">DVS<\/jats:styled-content>) was orally administrated to <jats:styled-content style=\"fixed-case\">UCMS<\/jats:styled-content> mice at the dose of 10\u00a0mg\/kg\/day 1\u00a0week before they went through a 7\u2010week stress procedure and lasted for over 8\u00a0weeks before the mice were killed. No significant changes were found for protein markers of neurons and astrocytes in <jats:styled-content style=\"fixed-case\">UCMS<\/jats:styled-content> mice. However, myelin and oligodendrocyte\u2010related proteins were significantly reduced in <jats:styled-content style=\"fixed-case\">UCMS<\/jats:styled-content> mice. <jats:styled-content style=\"fixed-case\">DVS<\/jats:styled-content> prevented the stress\u2010induced injury to white matter and the decrease of phosphorylated 5\u2032\u2010<jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content>\u2010activated protein kinase and 3\u2010hydroxy\u20103\u2010methyl\u2010glutaryl\u2010CoA reductase protein expression. <jats:styled-content style=\"fixed-case\">DVS<\/jats:styled-content> increased open arm entries in an elevated plus\u2010maze test, sucrose consumption in the sucrose preference test and decreased immobility in tail suspension and forced swimming tests. These findings suggest that stress induces depression\u2010like behaviors and white matter deficits in <jats:styled-content style=\"fixed-case\">UCMS<\/jats:styled-content> mice. <jats:styled-content style=\"fixed-case\">DVS<\/jats:styled-content> may ameliorate the oligodendrocyte dysfunction by affecting cholesterol synthesis, alleviating the depression\u2010like phenotypes in these mice.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12792-fig-0006-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nWe examined the possible role of oligodendrocyte and myelin in the pathological changes of depression with an unpredictable chronic mild stress (UCMS) mouse model. Oligodendrocyte\u2010related proteins in the mouse brain were specifically changed during the stress period. The depressive\u2010like behaviors and oligodendrocyte deficits could be prevented by the administration of desvenlafaxine. Oligodendrocyte and myelin may be an essential target of desvenlafaxine for the treatment of depression.<\/jats:p>","DOI":"10.1111\/jnc.12792","type":"journal-article","created":{"date-parts":[[2014,6,17]],"date-time":"2014-06-17T13:22:41Z","timestamp":1403011361000},"page":"229-238","source":"Crossref","is-referenced-by-count":43,"title":["Desvenlafaxine prevents white matter injury and improves the decreased phosphorylation of the rate\u2010limiting enzyme of cholesterol synthesis in a chronic mouse model of depression"],"prefix":"10.1111","volume":"131","author":[{"given":"Junhui","family":"Wang","sequence":"first","affiliation":[{"name":"Mental Health Center Shantou University Shantou Guangdong China"},{"name":"Department of Psychiatry Faculty of Medicine and Dentistry University of Alberta Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinping","family":"Qiao","sequence":"additional","affiliation":[{"name":"Mental Health Center Shantou 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