title: Desvenlafaxine prevents white matter injury and improves the decreased phosphorylation of the rate-limiting enzyme of cholesterol synthesis in a chronic mouse model of depression.
abstract: Serotonin/norepinephrine reuptake inhibitors antidepressants exert their effects by increasing serotonin and norepinephrine in the synaptic cleft. Studies show it takes 2-3 weeks for the mood-enhancing 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 (UCMS) mouse model. Desvenlafaxine (DVS) was orally administrated to UCMS mice at the dose of 10 mg/kg/day 1 week before they went through a 7-week stress procedure and lasted for over 8 weeks before the mice were killed. No significant changes were found for protein markers of neurons and astrocytes in UCMS mice. However, myelin and oligodendrocyte-related proteins were significantly reduced in UCMS mice. DVS prevented the stress-induced injury to white matter and the decrease of phosphorylated 5'-AMP-activated protein kinase and 3-hydroxy-3-methyl-glutaryl-CoA reductase protein expression. DVS increased open arm entries in an elevated plus-maze 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-like behaviors and white matter deficits in UCMS mice. DVS may ameliorate the oligodendrocyte dysfunction by affecting cholesterol synthesis, alleviating the depression-like phenotypes in these mice. We examined the possible role of oligodendrocyte and myelin in the pathological changes of depression with an unpredictable chronic mild stress (UCMS) mouse model. Oligodendrocyte-related proteins in the mouse brain were specifically changed during the stress period. The depressive-like 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.
authors.affiliation: Mental Health Center, Shantou University, Shantou, Guangdong, China.|Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Junhui
authors.initials: J
authors.lastname: Wang
authors.affiliation: Mental Health Center, Shantou University, Shantou, Guangdong, China.|Clinical Laboratory, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.|Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Jinping
authors.initials: J
authors.lastname: Qiao
authors.affiliation: Department of Psychiatry, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Clinical Psychiatry, Beijing Anding Hospital, Capital Medical University, Beijing, China.
authors.forename: Hongxing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Shenghua
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Mental Health Center, Shantou University, Shantou, Guangdong, China.
authors.forename: Handi
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Kelly
authors.initials: K
authors.lastname: Hartle
authors.affiliation: Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Huining
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Clinical Psychiatry, Beijing Anding Hospital, Capital Medical University, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jue
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Jiming
authors.initials: J
authors.lastname: Kong
authors.affiliation: Mental Health Center, Shantou University, Shantou, Guangdong, China.
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Li
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D002784:Cholesterol / Q000096:biosynthesis*; D003511:Cyclohexanols / Q000494:pharmacology / Q000627:therapeutic use*; D003863:Depression / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D000069468:Desvenlafaxine Succinate; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D066127:White Matter / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology
chemical_list: D000928:Antidepressive Agents; D003511:Cyclohexanols; D002784:Cholesterol; D000069468:Desvenlafaxine Succinate
keywords: depression; desvenlafaxine (DVS); myelin; oligodendrocyte; unpredictable chronic mild stress (UCMS)