The antipsychotic drug quetiapine stimulates oligodendrocyte differentiation by modulating the cell cycle. (September 2018)

• Record Type: Journal Article
• Authors: Mi, Guiyun; Wang, Yituo; Ye, Enmao; Gao, Yunyun; Liu, Qiaowei; Chen, Pinhong; Zhu, Yuyang; Yang, Hongju; Yang, Zheng
• Is Part Of: Neurochemistry international. Volume 118(2018)
• Page Start: 242
• Page End: 251
• Publication Date: 2018-09
• Subjects: Oligodendrocyte -- Cell cycle -- p21 -- Quetiapine -- PDGF -- Cuprizone; OPCs oligodendrocyte progenitor cells -- BrdU 5-Bromo-2′-deoxyuridine -- CDK cyclin-dependent kinase -- PDGF platelet-derived growth factor; Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2018.04.001
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: 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. Highlights: Quetiapine causes cell cycle exit and promotes cell differentiation in primary oligodendrocyte cultures. Chronic administration of quetiapine up-regulates the expression of the cyclin-dependent kinase inhibitor p21 in mice. Down-regulating p21 expression by RNA interference promotes oligodendrocyte proliferation and inhibits differentiation. Quetiapine may promote oligodendrocyte differentiation by modulating the cell cycle.