title: Quetiapine enhances oligodendrocyte regeneration and myelin repair after cuprizone-induced demyelination.
abstract: Myelin and oligodendrocyte dysfunctions have been consistently found in patients with schizophrenia. The effect of antipsychotics on myelin disturbances is unknown. The present study examined the effects of quetiapine on oligodendrocyte regeneration and myelin repair in a demyelination animal model. C57BL/6 mice were fed with cuprizone (0.2% w/w) for 12 weeks to induce chronic demyelination and oligodendrocyte degeneration, after which cuprizone was withdrawn to allow recovery. Quetiapine (10mg/kg/day) or vehicle (water) was administrated orally to mice for 0, 2, 3, or 4 weeks after cuprizone withdrawal. Locomotor activity and Y-maze tests were used to evaluate behavioral changes in the mice. Immunohistochemical staining was used to detect morphological and biological changes in the brains. Cuprizone administration for 12 weeks resulted in severe demyelination, locomotor hyperactivity, and working memory impairment in mice. Remyelination occurred when cuprizone was withdrawn. Quetiapine treatment during the recovery period significantly improved the spatial working memory and increased myelin restoration. Quetiapine treatment also enhanced the repopulation of mature oligodendrocytes in the demyelinated lesions, which was associated with down-regulation of transcription factor olig2 in the process of cell maturation. The results of this study demonstrated that quetiapine treatment during the recovery period improves spatial working memory and promotes oligodendrocyte development and remyelination. This study supports the role of oligodendrocyte dysfunction in memory deficits in a schizophrenia mouse model and suggests that quetiapine may target oligodendrocytes and improve cognitive function.
authors.affiliation: Department of Psychiatry, University of Saskatchewan, Saskatoon, SK, Canada.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Zhang
authors.forename: Handi
authors.initials: H
authors.lastname: Zhang
authors.forename: Lingyan
authors.initials: L
authors.lastname: Wang
authors.forename: Wengao
authors.initials: W
authors.lastname: Jiang
authors.forename: Haiyun
authors.initials: H
authors.lastname: Xu
authors.forename: Lan
authors.initials: L
authors.lastname: Xiao
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Bi
authors.forename: Junhui
authors.initials: J
authors.lastname: Wang
authors.forename: Shenghua
authors.initials: S
authors.lastname: Zhu
authors.forename: Ruiguo
authors.initials: R
authors.lastname: Zhang
authors.forename: Jue
authors.initials: J
authors.lastname: He
authors.forename: Qingrong
authors.initials: Q
authors.lastname: Tan
authors.forename: Dai
authors.initials: D
authors.lastname: Zhang
authors.forename: Jiming
authors.initials: J
authors.lastname: Kong
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Li
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D003471:Cuprizone / Q000494:pharmacology; D003711:Demyelinating Diseases / Q000139:chemically induced; D003987:Dibenzothiazepines / Q000494:pharmacology*; D004195:Disease Models, Animal; D008570:Memory, Short-Term / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009186:Myelin Sheath / Q000187:drug effects*; D009836:Oligodendroglia / Q000187:drug effects* / Q000502:physiology*; D000069348:Quetiapine Fumarate; D012038:Regeneration / Q000187:drug effects*; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D002614:Chelating Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D003471:Cuprizone