title: Olanzapine ameliorates neuropathological changes and increases IGF-1 expression in frontal cortex of C57BL/6 mice exposed to cuprizone.
abstract: Cuprizone (CPZ) induced demyelinating mouse has been used as an animal model to examine the assumed roles of altered oligodendrocytes in the pathophysiology and treatment of schizophrenia. The objectives of this study were to examine the effect of olanzapine, an atypical antipsychotic, on cuprizone-induced neuropathological changes in the frontal cortex of C57BL/6 mice, and to explore the underlying mechanism for the possible protective effects. The effects of six-week olanzapine (10 mg/kg/day) treatments on neuropathological changes were examined by immunohistochemistry and Western-blot analyses. Olanzapine treatment for six weeks effectively decreased the breakdown of myelin and oligodendrocytes loss of cuprizone-fed mice. Reactive cellular changes, including astrocyte gliosis, microglia accumulation and increased activation of oligodendrocyte progenitor cells, were also attenuated by olanzapine. However, the cortical expression level of insulin-like growth factor 1 (IGF-1) was significantly increased by olanzapine treatment in cuprizone-fed mice as measured by the quantitative real-time polymerase chain reaction (PCR) method. Olanzapine treatment in control mice consuming normal food had no effect on all above measures. These results provide the first in vivo evidence for the protective effects of olanzapine on cuprizone-induced neuropathological changes and suggest that up-regulated insulin-like growth factor 1 may contribute to the protective effects of this antipsychotic.
authors.affiliation: Mental Health Center, Shantou University Medical College, Shantou 515065, Guangdong, China.
authors.forename: Handi
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Mental Health Center, Shantou University Medical College, Shantou 515065, Guangdong, China.
authors.forename: Haiyun
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Cardiology, China-Japan Friendship Hospital of Jilin University, Jilin University, Chuangchun, Jilin, China.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Abulimiti
authors.initials: A
authors.lastname: Adilijiang
authors.affiliation: Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Junhui
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Kelly
authors.initials: K
authors.lastname: Hartle
authors.affiliation: Department of Neuropsychiatry, Affiliated ZhongDa Hospital Southeast University, Nanjing, Jiangsu, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of Mental Health, Peking University, Beijing, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi׳an, Shannxi, China.
authors.forename: Qingrong
authors.initials: Q
authors.lastname: Tan
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 Medical College, Shantou 515065, Guangdong, China. Electronic address: huangqj@stumhc.cn.
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Psychiatry, University of Alberta, Edmonton, Alberta, Canada. Electronic address: xinmin@ualberta.ca.
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Li
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects; D001569:Benzodiazepines / Q000494:pharmacology*; D003471:Cuprizone / Q000633:toxicity*; D003711:Demyelinating Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D005260:Female; D005625:Frontal Lobe / Q000166:cytology / Q000187:drug effects* / Q000473:pathology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects; D009186:Myelin Sheath / Q000378:metabolism; D000077152:Olanzapine; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012559:Schizophrenia / Q000188:drug therapy / Q000473:pathology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D003471:Cuprizone; D007334:Insulin-Like Growth Factor I; D000077152:Olanzapine
keywords: Atypical antipsychotic drugs; Demyelination; Myelin; Oligodendrocyte