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学科主题: 精神卫生
题名:
Quetiapine enhances oligodendrocyte regeneration and myelin repair after cuprizone-induced demyelination
作者: Zhang, Yanbo1,2; Zhang, Handi1; Wang, Lingyan3; Jiang, Wengao4; Xu, Haiyun5; Xiao, Lan6; Bi, Xiaoying7; Wang, Junhui1; Zhu, Shenghua1; Zhang, Ruiguo8; He, Jue1; Tan, Qingrong8; Zhang, Dai9; Kong, Jiming10; Li, Xin-Min1,10
关键词: Quetiapine ; Schizophrenia ; Oligodendrocyte ; Remyelination ; Cuprizone ; Olig2
刊名: SCHIZOPHRENIA RESEARCH
发表日期: 2012-06-01
DOI: 10.1016/j.schres.2012.04.006
卷: 138, 期:1, 页:8-17
收录类别: SCI ; SSCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Psychiatry
研究领域[WOS]: Psychiatry
关键词[WOS]: WHITE-MATTER ABNORMALITIES ; CENTRAL-NERVOUS-SYSTEM ; SPATIAL WORKING-MEMORY ; C57BL/6 MICE ; NEUROBIOLOGICAL CHANGES ; SUBVENTRICULAR ZONE ; MULTIPLE-SCLEROSIS ; BIPOLAR DISORDER ; PROGENITOR CELLS ; SCHIZOPHRENIA
英文摘要:

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/6mice 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(0.2% w/w) for 12 weeks to induce chronic demyelination and oligodendrocyte degeneration, after which cuprizone was withdrawn to allow recovery.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 (10 mg/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 Remyelination occurred when cuprizone was withdrawn.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. (C) 2012 Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: 2010DFB30820
项目资助者: Canadian Institutes of Health Research (CIHR) ; Ministry of Science and Technology (MOST) of the People&prime ; s Republic of China ; Saskatchewan Health Research Foundation (SHRF) ; AstraZeneca ; Pfizer Canada
WOS记录号: WOS:000304470200002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54065
Appears in Collections:北京大学精神卫生研究所_期刊论文

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作者单位: 1.Univ Manitoba, Fac Med, Dept Psychiat, Winnipeg, MB R3E 3N4, Canada
2.Univ Saskatchewan, Dept Psychiat, Saskatoon, SK S7N 0W0, Canada
3.Jilin Univ, China Japan Friendship Hosp, Dept Cardiol, Chuangchun, Jilin, Peoples R China
4.Wenzhou Med Coll, Neuropharmacol Lab, Wenzhou, Zhejiang, Peoples R China
5.Shantou Univ, Coll Med, Dept Anat, Shantou, Guangdong, Peoples R China
6.Third Mil Med Univ, Dept Histol & Embryol, Chongqing, Peoples R China
7.Second Mil Med Univ, Dept Neurol, Shanghai, Peoples R China
8.Fourth Mil Med Univ, Dept Psychiat, Xian 710032, Shanxi, Peoples R China
9.Peking Univ, Hlth Sci Ctr, Inst Mental Hlth, Beijing 100191, Peoples R China
10.Univ Manitoba, Dept Human Anat & Cell Sci, Winnipeg, MB R3E 3N4, Canada

Recommended Citation:
Zhang, Yanbo,Zhang, Handi,Wang, Lingyan,et al. Quetiapine enhances oligodendrocyte regeneration and myelin repair after cuprizone-induced demyelination[J]. SCHIZOPHRENIA RESEARCH,2012,138(1):8-17.
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