Recent studies have revealed that oligodendrocyte differentiation deficits and de-myelination occur in the brains of schizophrenic patients. Cell cycle proteins play a critical role in modulating oligodendrocyte proliferation and differentiation. In our previous studies, we found that cuprizone, a copper chelant, induces oligodendrocyte loss and demyelination, and this effect can be alleviated by using the atypical antipsychotic drug quetiapine. To explore the mechanisms of quetiapine in oligodendrocyte development, we examined the effects of quetiapine on cell cycle progression. Quetiapine promoted cell cycle exit and blocked the mitogenic effect of PDGF in cultured rat cortical oligodendrocyte progenitor cells (OPCs). Quetiapine accelerated OPC differentiation in vitro. Moreover, the systemic administration of quetiapine up-regulated p21 mRNA expression, a cyclin-dependent kinase inhibitor, in mice. Knocking down p21 expression by RNA interference enhanced proliferation and delayed differentiation. Our results suggest that cell cycle regulation may contribute to the differentiation-promoting effect of quetiapine.

最近的研究表明，精神分裂症患者的大脑中发生少突胶质细胞分化缺陷和脱髓鞘。细胞周期蛋白在调节少突胶质细胞的增殖和分化中起关键作用。在我们以前的研究中，我们发现铜螯合剂cuprizone引起少突胶质细胞损失和脱髓鞘，使用非典型的抗精神病药物喹硫平可以减轻这种作用。为了探索喹硫平在少突胶质细胞发育中的机制，我们研究了喹硫平对细胞周期进程的影响。喹硫平促进细胞周期退出并阻止PDGF在培养的大鼠皮质少突胶质祖细胞（OPC）中的促有丝分裂作用。喹硫平体外加速OPC分化。而且，喹硫平在小鼠中的全身性上调p21 mRNA表达（一种细胞周期蛋白依赖性激酶抑制剂）。通过RNA干扰抑制p21表达可增强增殖和延迟分化。我们的结果表明细胞周期调控可能有助于喹硫平的分化促进作用。