Luo Jia
Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, 132 Health Sciences Research Building, 1095 Veterans Drive, Lexington, KY, 40536, USA,
Cerebellum. 2015 Aug;14(4):383-5. doi: 10.1007/s12311-015-0674-8.
Alcohol abuse causes cerebellar dysfunction and cerebellar ataxia is a common feature in alcoholics. Alcohol exposure during development also impacts the cerebellum. Children with fetal alcohol spectrum disorder (FASD) show many symptoms associated specifically with cerebellar deficits. However, the cellular and molecular mechanisms are unclear. This special issue discusses the most recent advances in the study of mechanisms underlying alcoholinduced cerebellar deficits. The alteration in GABAA receptor-dependent neurotransmission is a potential mechanism for ethanol-induced cerebellar dysfunction. Recent advances indicate ethanol-induced increases in GABA release are not only in Purkinje cells (PCs), but also in molecular layer interneurons and granule cells. Ethanol is shown to disrupt the molecular events at the mossy fiber - granule cell - Golgi cell (MGG) synaptic site and granule cell parallel fibers - PCs (GPP) synaptic site, which may be responsible for ethanol-induced cerebellar ataxia. Aging and ethanol may affect the smooth endoplasmic reticulum (SER) of PC dendrites and cause dendritic regression. Ethanol withdrawal causes mitochondrial damage and aberrant gene modifications in the cerebellum. The interaction between these events may result in neuronal degeneration, thereby contributing to motoric deficit. Ethanol activates doublestranded RNA (dsRNA)-activated protein kinase (PKR) and PKR activation is involved ethanolinduced neuroinflammation and neurotoxicity in the developing cerebellum. Ethanol alters the development of cerebellar circuitry following the loss of PCs, which could result in modifications of the structure and function of other brain regions that receive cerebellar inputs. Lastly, choline, an essential nutrient is evaluated for its potential protection against ethanol-induced cerebellar damages. Choline is shown to ameliorate ethanol-induced cerebellar dysfunction when given before ethanol exposure.
酒精滥用会导致小脑功能障碍，小脑共济失调是酗酒者的常见特征。发育过程中接触酒精也会影响小脑。患有胎儿酒精谱系障碍（FASD）的儿童表现出许多与小脑缺陷相关的症状。然而，其细胞和分子机制尚不清楚。本期特刊讨论了酒精诱导小脑缺陷潜在机制研究的最新进展。GABAA受体依赖性神经传递的改变是乙醇诱导小脑功能障碍的一种潜在机制。最新进展表明，乙醇诱导的GABA释放增加不仅发生在浦肯野细胞（PCs）中，也发生在分子层中间神经元和颗粒细胞中。乙醇被证明会破坏苔藓纤维-颗粒细胞-高尔基细胞（MGG）突触部位和颗粒细胞平行纤维-浦肯野细胞（GPP）突触部位的分子事件，这可能是乙醇诱导小脑共济失调的原因。衰老和乙醇可能会影响PC树突的滑面内质网（SER），并导致树突退化。乙醇戒断会导致小脑线粒体损伤和基因异常修饰。这些事件之间的相互作用可能导致神经元变性，从而导致运动功能障碍。乙醇激活双链RNA（dsRNA）激活蛋白激酶（PKR），PKR激活参与乙醇诱导的发育中小脑的神经炎症和神经毒性。乙醇会在PCs缺失后改变小脑回路的发育，这可能会导致接受小脑输入的其他脑区的结构和功能发生改变。最后，对一种必需营养素胆碱对乙醇诱导小脑损伤的潜在保护作用进行了评估。结果表明，在接触乙醇之前给予胆碱可改善乙醇诱导的小脑功能障碍。
