Quetiapine Modulates Histone Methylation Status in Oligodendroglia and Rescues Adolescent Behavioral Alterations of Socially Isolated Mice
Quetiapine Modulates Histone Methylation Status in Oligodendroglia and Rescues Adolescent Behavioral Alterations of Socially Isolated Mice
复制标题
喹硫平调节少突胶质细胞的组蛋白甲基化状态并拯救社会孤立小鼠的青春期行为改变
DOI：
10.3389/fpsyt.2019.00984
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发表时间：
2020-01-31
影响因子：
4.7
通讯作者：
Xiao, Lan
中科院分区：
文献类型：
--
作者：
Chen, Xianjun;Liu, Hao;Xiao, Lan
前额叶皮层中的表观遗传改变和少突胶质髓鞘形成受损已被证明与社会剥夺中的行为和认知功能障碍相关。我们以前的研究表明，非典型抗精神病药奎替鲁胺可以促进少突胶质细胞分化和髓鞘形成。然而，quetioline是否以及如何在调节少突胶质细胞中的异常表观遗传改变和减轻社会隔离的行为改变中有益尚不清楚。在这项研究中，对处于轻度社会隔离应激状态的青春期小鼠经口给予奎替鲁。我们首次证实，在一个新的青春期的社会隔离可能会损害社交能力，但不是运动行为的小鼠。此外，奎替鲁胺减轻髓鞘缺陷，并增加组蛋白甲基化水平（H3K9me3）在成熟的少突胶质细胞在社会隔离的小鼠前额叶皮层。令人惊讶的是，奎替鲁治疗显著增加了运动活动，并成功逆转了社交孤立小鼠的社交回避行为。综上所述，我们的数据表明，奎替鲁肽可能通过调节表观遗传状态向少突胶质细胞成熟的有益方向拯救社会隔离中的行为变化，为奎替鲁肽治疗精神疾病的药理机制提供了新的见解。
Epigenetic alterations and impaired oligodendroglial myelination in the prefrontal cortex have been shown to correlate with behavioral and cognitive dysfunctions in social deprivation. Our previous study demonstrated that quetiapine, an atypical antipsychotic, could promote oligodendroglial differentiation and myelination. However, whether and how quetiapine could be beneficial in modulating aberrant epigenetic alterations in oligodendroglial cells and relieving behavioral alterations from social isolation is unknown. In this study, quetiapine was orally administered in adolescent mice undergoing mild stress of social isolation. We firstly confirmed that social isolation during a novel adolescent period could impair sociability, but not locomotive behaviors in mice. Moreover, quetiapine alleviated myelin deficits, and increased levels of histone methylation (H3K9me3) in mature oligodendroglia in the prefrontal cortex of socially isolated mice. Strikingly, quetiapine treatment significantly increased locomotive activity, and successfully reversed social avoidance behavior of the socially isolated mice. Taken together, our data suggest that quetiapine may rescue behavioral changes from social isolation through modulating epigenetic status toward the beneficial direction for oligodendroglial maturation, providing new insights into the pharmacological mechanism of quetiapine for mental illnesses.