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 deleted Olig2 in oligodendroglial lineage cells (Olig2 cKO) and screened the behavioral changes in adult mice. We found that Olig2 ablation impaired myelin development, which further resulted in severe hypomyelination in the anterior cingulate cortex. Strikingly, Olig2 cKO mice exhibited an anxious phenotype, aberrant responses to stress, and cognitive deficits. Moreover, Olig2 cKO 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.

中文翻译：

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Olig2缺乏症引起的髓磷脂缺乏症导致认知功能障碍，并增加成年小鼠社交退缩的脆弱性。

少突胶质细胞（OL）和髓磷脂的发育对于网络整合至关重要，并且与更高的大脑功能有关。越来越多的证据表明在严重的精神疾病中OL和髓磷脂的结构和功能受损。但是，这些缺陷是否导致脑功能障碍或此类疾病的发病机制仍缺乏直接证据。在这项研究中，我们有条件地删除Olig2的在少突胶质细胞系细胞（Olig2的CKO）和筛选成年小鼠的行为变化。我们发现，Olig2切除会损害髓磷脂的发育，进而导致前扣带回皮质的严重髓鞘减少。令人惊讶的是，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，在社会孤立的轻度压力下，Olig2 cKO小鼠表现出更大的社交回避脆弱性。总之，这些结果表明OL和髓磷脂的发育缺陷会导致认知障碍，并增加令人联想到精神疾病的表型风险。