Haloperidol activates quiescent oligodendroglia precursor cells in the adult mouse brain

Haloperidol activates quiescent oligodendroglia precursor cells in the adult mouse brain
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氟哌啶醇激活成年小鼠大脑中静止的少突胶质细胞前体细胞

DOI:
10.1016/j.schres.2010.02.1068
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发表时间:
2010-06
影响因子:
4.5
通讯作者:
Cai, Wenqin
Cai, Wenqin
中科院分区:
医学2区
文献类型:
--
作者:
Kong, Jiming;Wang, Hanzhi;Li, Xinmin;Xu, Haiyun;Mei, Feng;Xiao, Lan;Niu, Jianqin;Cai, Wenqin

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最近的人类研究表明,少突胶质细胞(OLs)的异常发育是精神分裂症病理生理的一个重要组成部分。然而,关于抗精神病药物对OLs发展的影响的信息较少。在本研究中,年轻的成年C57BL/6小鼠在其饮用水中给予氟哌啶醇(HAL; 2mg/kg/天)3或6周。药物治疗结束后,处死小鼠,定量测定胼胝体、海马和大脑皮层脑区表达NG2-和olig2的细胞数量。NG2是少突胶质前体细胞(OPCs)的特异性标志物;Olig2标记胶质祖细胞。HAL处理3周后,胼胝体中表达ng2的细胞数量增加;HAL治疗3周和6周增加了所有三个脑区中表达Olig2的细胞数量,并增加了相同脑区中Olig2的表达水平。这些结果表明,HAL处理激活了成体OPCs,在正常条件下,OPCs很少分裂,但通过增殖和分化对各种侮辱因子作出反应。然而,我们进一步观察发现,在hal处理的小鼠中,成熟OLs的数量和髓鞘碱性蛋白的数量没有变化,这表明药物治疗对OLs的成熟没有影响。此外,HAL治疗并没有增加GFAP-和cd68表达细胞的数量,这表明当药物激活成人大脑中静止的OPCs时,没有发生胶质瘤和炎症反应。这些结果表明HAL治疗可能针对OLs的发展。
Recent human studies suggest that abnormal development of oligodendrocytes (OLs) is an important component in the pathophysiology of schizophrenia. However, less information is available regarding effects of antipsychotics on OLs' development. In the present study, young adult C57BL/6 mice were given haloperidol (HAL; 2mg/kg/day) in their drinking water for three or six weeks. At the conclusion of the drug treatment, mice were sacrificed and the numbers of NG2- and Olig2-expressing cells in the brain regions of the corpus callosum, hippocampus and cerebral cortex were quantified. NG2 is a specific marker for oligodendroglia precursor cells (OPCs); Olig2 marks glial progenitors. HAL treatment for three weeks increased the number of NG2-expressing cells in the corpus callosum; HAL treatment for three and six weeks increased the numbers of Olig2-expressing cells in all three brain regions and increased the levels of Olig2 expression in the same brain regions. These results suggest that HAL treatment activates adult OPCs, which divide infrequently under normal conditions but respond to a variety of insulting factors by proliferation and differentiation. However, our further observations showed no changes in the number of mature OLs and the amount of myelin basic protein in HAL-treated mice, suggesting the drug treatment has no effect on the maturation of OLs. In addition, HAL treatment did not increase the numbers of GFAP- and CD68-expressing cells, suggesting that no gliosis and inflammatory responses occurred while the drug activated the quiescent OPCs in adult brain. These results suggest that HAL treatment may target the development of OLs.
喹硫平减轻 C57BL/6 小鼠大脑中铜宗诱导的白质病理
DOI: 10.1016/j.schres.2008.09.013
发表时间: 2008-12
影响因子: 4.5
作者:
Li, Xin-Min;Jiang, Wengao;Li, Xiaokun;Xiao, Lan;Yan, Bin;Wang, Yanlin;Bi, Xiaoying;Kong, Jiming;Xu, Haiyun;Zhang, Yanbo;He, Jue
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DOI: 10.1016/j.surg.2008.05.017
发表时间: 2008-11
期刊: SURGERY
影响因子: 3.8
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发表时间: 2003-03-01
影响因子: 10.6
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发表时间: 1998-08-01
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