Department of Neuroscience, Del Monte Institute for Neuroscience, University of Rochester Medical Center, Rochester, NY, USA.
Neuroscience Graduate Program, University of Rochester Medical Center, Rochester, NY, USA.
Eur J Neurosci. 2021 Sep;54(5):5834-5843. doi: 10.1111/ejn.14706. Epub 2020 Feb 28.
Alcohol use is highly prevalent in modern society and ramifications of alcohol abuse pose a large public health concern. Previous work investigating the effects of alcohol exposure on the brain has implicated microglia, the resident immune cells of the central nervous system (CNS), as critical participants in the brain's response to chronic and developmental ethanol (EtOH) exposure. As rapid sensors of their environment, microglia also have the capacity to rapidly respond to alcohol administration and to contribute to acute effects of alcohol on the brain; however, their acute responses have not been assessed. Here, for the first time, we have examined the acute response of microglia to alcohol intoxication in vivo utilizing two-photon microscopy to assess the dynamics of these motile cells in both visual cortex and the cerebellum of mice. We found that microglia respond rapidly to EtOH exposure with fast changes in morphology, motility, parenchyma surveillance, and injury response. However, regional differences between the responses of cerebellar and cortical microglial populations indicate that subtle differences in microglial physiology may alter their vulnerability to acute alcohol intoxication. Our findings suggest that the longer-term effects of repeated EtOH exposure on microglia may result from repeat acute alterations in microglial physiology by single exposure to alcohol which rapidly alter behavior in specific microglial populations.
在现代社会中,酒精的使用非常普遍,而酒精滥用的后果给公共健康带来了巨大的关注。先前的研究表明,酒精暴露对大脑的影响涉及小胶质细胞,即中枢神经系统(CNS)的固有免疫细胞,它们是大脑对慢性和发育性乙醇(EtOH)暴露反应的关键参与者。作为其环境的快速传感器,小胶质细胞也能够快速响应酒精的摄入,并对大脑的急性酒精作用产生影响;然而,它们的急性反应尚未被评估。在这里,我们首次利用双光子显微镜在体内检查了小胶质细胞对酒精中毒的急性反应,以评估这些运动细胞在小鼠视觉皮层和小脑中的动力学。我们发现,小胶质细胞对 EtOH 暴露的反应迅速,形态、运动性、实质监测和损伤反应都发生了快速变化。然而,小脑和皮质小胶质细胞群体反应之间的区域差异表明,小胶质细胞生理学的细微差异可能改变它们对急性酒精中毒的易感性。我们的研究结果表明,重复 EtOH 暴露对小胶质细胞的长期影响可能是由于单次酒精暴露对小胶质细胞生理学的反复急性改变导致的,这种改变会迅速改变特定小胶质细胞群体的行为。