Abstract
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.
Highlights
Alcohol consumption has been linked to long-term and severe brain dysfunctions
Since the adult CNS is enriched with dense myelin sheaths, we set out to examine whether chronic alcohol exposure could change myelin density, the 6-month-old mice were introduced to alcohol for 3 weeks (Figure 1A)
We immunostained for MBP on the brain sections with or without alcohol exposure and our result indicated that the MBP + myelin area or intensity was not significantly altered in the cortex and corpus callosum of the 5 or 10% alcohol treated brains as compared to the vehicle controls (Figures 1B,D), suggesting that chronic alcohol exposure may not cause overt myelin loss
Summary
Alcohol consumption has been linked to long-term and severe brain dysfunctions. In addition to the alternations in neurotransmitter level and neuronal structural change (Davis and Wu, 2001; Romero et al, 2013; Abrahao et al, 2017), MRI imaging indicated alcohol-related abnormalities in the white matter (Monnig et al, 2015). Alcohol Consumption Inhibits Adulthood Myelinogenesis white matter integrity is susceptible to alcohol exposure especially during fetal and adolescent stage (Pascual et al, 2014; Vargas et al, 2014; Rice and Gu, 2019). The white matter is composed of abundant axons wrapped with myelin sheaths, the multiple concentric cell membranes that are generated by oligodendrocytes (OLs) in the CNS. Myelin sheaths insulate axons and ensure fast action potential propagation along the axon (Zalc and Colman, 2000; Nave and Werner, 2014; Seidl, 2014)
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