Myelin Deficits Caused by Olig2 Deficiency Lead to Cognitive Dysfunction and Increase Vulnerability to Social Withdrawal in Adult Mice
Myelin Deficits Caused by Olig2 Deficiency Lead to Cognitive Dysfunction and Increase Vulnerability to Social Withdrawal in Adult Mice
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Olig2 缺乏引起的髓磷脂缺陷会导致成年小鼠认知功能障碍并增加社交退缩的脆弱性
DOI：
10.1007/s12264-019-00449-7
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发表时间：
2019-11-22
影响因子：
5.6
通讯作者：
Xiao, Lan
中科院分区：
文献类型：
--
作者：
Chen, Xianjun;Wang, Fei;Xiao, Lan
少突胶质细胞（OL）和髓鞘发育对于网络整合至关重要，并与高级脑功能相关。越来越多的证据表明，严重的精神疾病中的OL和髓鞘的结构和功能受损。然而，这些缺陷是否有助于脑功能障碍或此类疾病的发病机制仍然缺乏直接证据。在本研究中，我们在少突胶质细胞谱系细胞中条件性缺失Olig2（Olig2cKO），并筛选成年小鼠的行为变化。我们发现Olig2消融损害了髓鞘的发育，这进一步导致了前扣带皮层严重的髓鞘形成不足。引人注目的是，Olig2cKO小鼠表现出焦虑表型、对压力的异常反应和认知缺陷。此外，Olig2cKO小鼠在社交孤立的轻度压力下表现出对社交回避的脆弱性增加。总之，这些结果表明，OL和髓鞘的发育缺陷导致认知障碍，并增加了精神疾病表型的风险。
Oligodendrocyte (OL) and myelin development are crucial for network integration and are associated with higher brain functions. Accumulating evidence has demonstrated structural and functional impairment of OLs and myelin in serious mental illnesses. However, whether these deficits contribute to the brain dysfunction or pathogenesis of such diseases still lacks direct evidence. In this study, we conditionally deletedOlig2in oligodendroglial lineage cells (Olig2cKO) and screened the behavioral changes in adult mice. We found thatOlig2ablation impaired myelin development, which further resulted in severe hypomyelination in the anterior cingulate cortex. Strikingly,Olig2cKO mice exhibited an anxious phenotype, aberrant responses to stress, and cognitive deficits. Moreover,Olig2cKO mice showed increased vulnerability to social avoidance under the mild stress of social isolation. Together, these results indicate that developmental deficits in OL and myelin lead to cognitive impairment and increase the risk of phenotypes reminiscent of mental illnesses.