Haloperidol promotes proliferation but inhibits differentiation in rat oligodendrocyte progenitor cell cultures
Haloperidol promotes proliferation but inhibits differentiation in rat oligodendrocyte progenitor cell cultures
复制标题
氟哌啶醇促进大鼠少突胶质祖细胞培养物的增殖但抑制分化
DOI：
10.1139/o09-178
复制
发表时间：
2010-08-01
影响因子：
2.9
通讯作者：
Xiao, Lan
中科院分区：
文献类型：
--
作者：
Niu, Jianqin;Mei, Feng;Xiao, Lan
氟哌啶醇是一种常用的典型抗精神病药物，对阳性症状有很强的作用，但对精神分裂症的治疗作用较小。甚至可能加重精神分裂症患者的阴性症状和认知障碍。少突胶质细胞的丢失被认为是精神分裂症阴性症状的一个相关因素。最近的研究表明，慢性氟哌啶醇治疗诱导了小鼠某些脑区少突胶质细胞相关基因的下调。在本研究中，我们使用出生后1-3天大鼠的原代少突胶质前体细胞培养，观察氟哌啶醇对少突胶质前体细胞增殖和分化的直接影响。结果表明：(1)氟哌啶醇(0~100mU·L~(-1))促进少突胶质前体细胞的增殖。(2)慢性氟哌啶醇(0.5mU/L L-1)可使髓鞘碱性蛋白阳性的少突胶质细胞减少，形成髓鞘样膜的少突胶质细胞减少，从而抑制少突胶质细胞的终末分化。在少突胶质细胞前体细胞中检测到D3受体mRNA，氟哌啶醇治疗后D3受体mRNA表达下调。这些结果表明，典型的抗精神病药物氟哌啶醇影响少突胶质前体细胞的发育，可能涉及D3受体下调。我们的观察为了解典型抗精神病药物副作用的可能细胞机制提供了新的见解，并支持少突胶质细胞异常可能参与精神分裂症的发病机制。
Haloperidol is a commonly used, typical, antipsychotic drug (APD) that acts strongly against positive symptoms, but has fewer therapeutic effects on. or may even aggravate, negative symptoms and cognitive deficits in patients with schizophrenia. Loss of oligodendrocytes has been suggested as a factor associated with the negative symptoms of schizophrenia. Recent study shows that chronic haloperidol treatment induced down-regulation of oligodendrocyte-related genes in certain brain regions of mouse. In this study, we used primary oligodendrocyte progenitor cell cultures from 1- to 3-day-postnatal rats to investigate the direct effects of haloperidol on the proliferation and differentiation of oligodendrocyte progenitor cells. Our results showed that (i) haloperidol (0-100 mu mol.L-1) facilitated the proliferation of oligodendrocyte progenitor cells. (ii) chronic haloperidol (0 5 mu mol L-1) treatment decreased the number of myelin basic protein positive oligodendrocytes and reduced the oligodendrocytes cells possessing myelin-like membranes, resulting in inhibition of the terminal differentiation of oligodendrocytes. and (iii) D3 receptor mRNA was detected in oligodendrocyte progenitor cells, and haloperidol treatment induced a down-regulation of D3 receptor mRNA These results suggest that the typical antipsychotic drug haloperidol affects the development of oligodendrocyte progenitor cells, and that D3 receptor down regulation may be involved Our observations provide new insight into possible cellular mechanisms responsible for the side effects of typical ant psychotic drugs and support the concept that abnormality of oligodendrocytes may be involved in the pathogenesis of schizophrenia