Guo Feng, Zhang Yi-Fan, Liu Kun, Huang Xu, Li Rui-Xue, Wang Shu-Yue, Wang Fei, Xiao Lan, Mei Feng, Li Tao
Brain and Intelligence Research Key Laboratory of Chongqing Education Commission, Department of Histology and Embryology, Third Military Medical University (Army Medical University), Chongqing, China.
The First Camp of Cadet Brigade, School of Basic Medicine, Third Military Medical University (Army Medical University), Chongqing, China.
Front Cell Neurosci. 2021 Aug 27;15:732602. doi: 10.3389/fncel.2021.732602. eCollection 2021.
Chronic alcohol consumption causes cognitive impairments accompanying with white matter atrophy. Recent evidence has shown that myelin dynamics remain active and are important for brain functions in adulthood. For example, new myelin generation is required for learning and memory functions. However, it remains undetermined whether alcohol exposure can alter myelin dynamics in adulthood. In this study, we examine the effect of chronic alcohol exposure on myelin dynamics by using genetic approaches to label newly generated myelin (NG2-CreERt; mT/mG). Our results indicated that alcohol exposure (either 5% or 10% in drinking water) for 3 weeks remarkably reduced mGFP + /NG2- new myelin and mGFP + /CC1 + new oligodendrocytes in the prefrontal cortex and corpus callosum of 6-month-old NG2-CreERt; mT/mG mice as compared to controls without changing the mGFP + /NG2 + oligodendrocyte precursor cells (OPCs) density, suggesting that alcohol exposure may inhibit oligodendrocyte differentiation. In support with these findings, the alcohol exposure did not significantly alter apoptotic cell number or overall MBP expression in the brains. Further, the alcohol exposure decreased the histone deacetylase1 (HDAC1) expression in mGFP + /NG2 + OPCs, implying epigenetic mechanisms were involved in the arrested OPC differentiation. Together, our results indicate that chronic exposure to alcohol can inhibit myelinogenesis in the adult mouse brain and that may contribute to alcohol-related cognitive impairments.
长期饮酒会导致认知障碍并伴有白质萎缩。最近的证据表明，髓鞘动力学在成年期仍保持活跃，并且对脑功能很重要。例如，学习和记忆功能需要新的髓鞘生成。然而，酒精暴露是否会改变成年期的髓鞘动力学仍未确定。在本研究中，我们通过使用基因方法标记新生成的髓鞘（NG2-CreERt；mT/mG）来研究慢性酒精暴露对髓鞘动力学的影响。我们的结果表明，与对照组相比，6个月大的NG2-CreERt；mT/mG小鼠饮用含5%或10%酒精的水3周后，前额叶皮质和胼胝体中mGFP + /NG2-新髓鞘和mGFP + /CC1 +新少突胶质细胞显著减少，而mGFP + /NG2 +少突胶质前体细胞（OPC）密度未改变，这表明酒精暴露可能抑制少突胶质细胞分化。支持这些发现的是，酒精暴露并未显著改变大脑中的凋亡细胞数量或整体髓鞘碱性蛋白（MBP）表达。此外，酒精暴露降低了mGFP + /NG2 + OPCs中组蛋白脱乙酰基酶1（HDAC1）的表达，这意味着表观遗传机制参与了OPC分化的停滞。总之，我们的结果表明，慢性酒精暴露可抑制成年小鼠大脑中的髓鞘生成，这可能导致与酒精相关的认知障碍。
