Bazzi Sam A, Maguire Cole, Mayfield R Dayne, Melamed Esther
Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
Department of Neuroscience, The University of Texas at Austin, Austin, TX, USA.
Addict Biol. 2025 Feb;30(2):e70012. doi: 10.1111/adb.70012.
Oligodendrocytes are a key cell type within the central nervous system (CNS) that generates the myelin sheath covering axons, enabling fast propagation of neuronal signals. Alcohol consumption is known to affect oligodendrocytes and white matter in the CNS. However, most studies have focused on foetal alcohol spectrum disorder and severe alcohol use disorder. Additionally, the impact of alcohol dosage on oligodendrocytes has not been previously investigated. In this study, we evaluated transcriptomic changes in C57BL6/J cultured mature oligodendrocytes following exposure to moderate and high concentrations of alcohol. We found that high concentrations of alcohol elicited gene expression changes across a wide range of biological pathways, including myelination, protein translation, integrin signalling, cell cycle regulation and inflammation. Further, our results demonstrate that transcriptomic changes are indeed dependent on alcohol concentration, with moderate and high concentrations of alcohol provoking distinct gene expression profiles. In conclusion, our study demonstrates that alcohol-induced transcriptomic changes in oligodendrocytes are concentration-dependent and may have critical downstream impacts on myelin production. Targeting alcohol-induced changes in cell cycle regulation, integrin signalling, inflammation or protein translation regulation may uncover mechanisms for modulating myelin production or inhibition. Furthermore, gaining a deeper understanding of alcohol's effects on oligodendrocyte demyelination and remyelination could help uncover therapeutic pathways that can be utilized independently of alcohol to aid in remyelinating drug design.
少突胶质细胞是中枢神经系统（CNS）中的一种关键细胞类型，它能产生覆盖轴突的髓鞘，使神经元信号得以快速传播。已知饮酒会影响中枢神经系统中的少突胶质细胞和白质。然而，大多数研究都集中在胎儿酒精谱系障碍和严重酒精使用障碍上。此外，酒精剂量对少突胶质细胞的影响此前尚未得到研究。在本研究中，我们评估了C57BL6/J培养的成熟少突胶质细胞在暴露于中度和高浓度酒精后的转录组变化。我们发现，高浓度酒精引发了广泛生物途径中的基因表达变化，包括髓鞘形成、蛋白质翻译、整合素信号传导、细胞周期调控和炎症。此外，我们的结果表明，转录组变化确实依赖于酒精浓度，中度和高浓度酒精引发了不同的基因表达谱。总之，我们的研究表明，酒精诱导的少突胶质细胞转录组变化是浓度依赖性的，可能对髓鞘生成产生关键的下游影响。针对酒精诱导的细胞周期调控、整合素信号传导、炎症或蛋白质翻译调控的变化，可能会揭示调节髓鞘生成或抑制的机制。此外，更深入地了解酒精对少突胶质细胞脱髓鞘和再髓鞘化的影响，有助于揭示可独立于酒精用于辅助再髓鞘化药物设计的治疗途径。
