School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China.
Ningxia Key Laboratory of Cerebrocranial Diseases, Ningxia Medical University, Yinchuan, China.
Brain Behav. 2020 Jun;10(6):e01623. doi: 10.1002/brb3.1623. Epub 2020 May 3.
The low number of oligodendrocytes (OLs) in the hippocampus of patients with schizophrenia suggests that hippocampal demyelination is changed in this condition. Sox10 is expressed throughout OL development. The effect of Sox10 on myelin regeneration is unknown. This study aimed to analyze changes in Sox10 expression in the hippocampus and its regulatory role in hippocampal myelin regeneration in a mouse model of demyelination.
Mice were fed 0.2% cuprizone (CPZ) for six weeks to establish the acute demyelinating model (CPZ mice). Behavioral changes of these mice were assessed via open field and tail suspension tests. The ultrastructure of the myelin sheaths in the hippocampus was observed by transmission electron microscopy. The expression levels of myelin sheath-related proteins and the transcription factor Sox10 were detected via immunohistochemistry and Western blots. Furthermore, Sox10-overexpressing adeno-associated virus was injected into the hippocampus after establishing the demyelinating model to investigate effects of Sox10 on remyelination.
CPZ mice showed abnormal behavioral changes, a large number of pathological changes in the myelin sheaths, and significantly reduced protein expression of the myelin sheath markers myelin basic protein and proteolipid protein. This confirmed that the demyelinating model was successfully established. Meanwhile, the protein expression of the oligodendrocyte precursor cell marker neural/glial antigen 2 (NG2) increased, whereas Sox10 expression decreased. After Sox10 overexpression in the hippocampus, the abnormal behavior was improved, the ultrastructure of the myelin sheaths was restored, and the expression of myelin sheath protein was reversed. NG2 expression was upregulated.
Overexpression of Sox10 promotes hippocampal remyelination after CPZ-induced acute demyelination.
精神分裂症患者海马区少突胶质细胞（OLs）数量减少表明，这种情况下海马脱髓鞘发生改变。 Sox10 在 OL 发育过程中均有表达。 Sox10 对髓鞘再生的影响尚不清楚。本研究旨在分析脱髓鞘模型小鼠海马 Sox10 表达的变化及其对海马髓鞘再生的调节作用。
用 0.2%的 Cuprizone（CPZ）喂养小鼠 6 周，建立急性脱髓鞘模型（CPZ 小鼠）。通过旷场和悬尾实验评估这些小鼠的行为变化。透射电镜观察海马髓鞘超微结构。免疫组化和 Western blot 检测髓鞘相关蛋白和转录因子 Sox10 的表达水平。此外，在建立脱髓鞘模型后，将 Sox10 过表达的腺相关病毒注入海马，以研究 Sox10 对髓鞘再生的影响。
CPZ 小鼠表现出异常的行为变化、大量的髓鞘病理改变，以及髓鞘标志物髓鞘碱性蛋白和蛋白脂蛋白的蛋白表达显著降低。这证实了脱髓鞘模型的成功建立。同时，少突胶质前体细胞标志物神经/神经胶质抗原 2（NG2）的蛋白表达增加，而 Sox10 表达减少。过表达海马 Sox10 后，异常行为得到改善，髓鞘超微结构得到恢复，髓鞘蛋白表达得到逆转。NG2 表达上调。
CPZ 诱导的急性脱髓鞘后，Sox10 的过表达促进了海马的髓鞘再生。
