Wilhelm Clare J, Guizzetti Marina
Research Service, VA Portland Health Care SystemPortland, OR, USA; Department of Psychiatry, Oregon Health and Science UniversityPortland, OR, USA.
Research Service, VA Portland Health Care SystemPortland, OR, USA; Department of Behavioral Neuroscience, Oregon Health and Science UniversityPortland, OR, USA.
Front Integr Neurosci. 2016 Jan 11;9:65. doi: 10.3389/fnint.2015.00065. eCollection 2015.
Alcohol consumption during pregnancy can produce a variety of central nervous system (CNS) abnormalities in the offspring resulting in a broad spectrum of cognitive and behavioral impairments that constitute the most severe and long-lasting effects observed in fetal alcohol spectrum disorders (FASD). Alcohol-induced abnormalities in glial cells have been suspected of contributing to the adverse effects of alcohol on the developing brain for several years, although much research still needs to be done to causally link the effects of alcohol on specific brain structures and behavior to alterations in glial cell development and function. Damage to radial glia due to prenatal alcohol exposure may underlie observations of abnormal neuronal and glial migration in humans with Fetal Alcohol Syndrome (FAS), as well as primate and rodent models of FAS. A reduction in cell number and altered development has been reported for several glial cell types in animal models of FAS. In utero alcohol exposure can cause microencephaly when alcohol exposure occurs during the brain growth spurt a period characterized by rapid astrocyte proliferation and maturation; since astrocytes are the most abundant cells in the brain, microenchephaly may be caused by reduced astrocyte proliferation or survival, as observed in in vitro and in vivo studies. Delayed oligodendrocyte development and increased oligodendrocyte precursor apoptosis has also been reported in experimental models of FASD, which may be linked to altered myelination/white matter integrity found in FASD children. Children with FAS exhibit hypoplasia of the corpus callosum and anterior commissure, two areas requiring guidance from glial cells and proper maturation of oligodendrocytes. Finally, developmental alcohol exposure disrupts microglial function and induces microglial apoptosis; given the role of microglia in synaptic pruning during brain development, the effects of alcohol on microglia may be involved in the abnormal brain plasticity reported in FASD. The consequences of prenatal alcohol exposure on glial cells, including radial glia and other transient glial structures present in the developing brain, astrocytes, oligodendrocytes and their precursors, and microglia contributes to abnormal neuronal development, reduced neuron survival and disrupted brain architecture and connectivity. This review highlights the CNS structural abnormalities caused by in utero alcohol exposure and outlines which abnormalities are likely mediated by alcohol effects on glial cell development and function.
孕期饮酒会使后代出现各种中枢神经系统（CNS）异常，导致一系列认知和行为障碍，这些障碍构成了胎儿酒精谱系障碍（FASD）中观察到的最严重且持久的影响。多年来，人们一直怀疑酒精诱导的神经胶质细胞异常是酒精对发育中大脑产生不良影响的原因之一，尽管仍需开展大量研究来建立酒精对特定脑结构和行为的影响与神经胶质细胞发育及功能改变之间的因果联系。产前酒精暴露导致的放射状胶质细胞损伤，可能是胎儿酒精综合征（FAS）患者以及FAS的灵长类和啮齿类动物模型中观察到的神经元和神经胶质细胞迁移异常的原因。在FAS动物模型中，已报道几种神经胶质细胞类型的细胞数量减少且发育改变。当在脑生长突增期（其特征为星形胶质细胞快速增殖和成熟）发生酒精暴露时，子宫内酒精暴露可导致小头畸形；由于星形胶质细胞是大脑中数量最多的细胞，小头畸形可能是由星形胶质细胞增殖或存活减少所致，这在体外和体内研究中均有观察到。在FASD实验模型中也报道了少突胶质细胞发育延迟和少突胶质细胞前体细胞凋亡增加，这可能与FASD儿童中发现的髓鞘形成/白质完整性改变有关。FAS儿童表现出胼胝体和前连合发育不全，这两个区域需要神经胶质细胞的引导和少突胶质细胞的正常成熟。最后，发育过程中的酒精暴露会破坏小胶质细胞功能并诱导小胶质细胞凋亡；鉴于小胶质细胞在大脑发育过程中的突触修剪作用，酒精对小胶质细胞的影响可能与FASD中报道的异常脑可塑性有关。产前酒精暴露对神经胶质细胞的影响，包括发育中大脑中存在的放射状胶质细胞和其他短暂性神经胶质结构、星形胶质细胞、少突胶质细胞及其前体细胞以及小胶质细胞，会导致神经元发育异常、神经元存活减少以及脑结构和连接性破坏。本综述强调了子宫内酒精暴露引起的中枢神经系统结构异常，并概述了哪些异常可能是由酒精对神经胶质细胞发育和功能的影响介导的。
