Glia and Neurodevelopment: Focus on Fetal Alcohol Spectrum Disorders

Abstract

During the last 20 years, new and exciting roles for glial cells in brain development have been described. Moreover, several recent studies implicated glial cells in the pathogenesis of neurodevelopmental disorders including Down syndrome, Fragile X syndrome, Rett Syndrome, Autism Spectrum Disorders, and Fetal Alcohol Spectrum Disorders (FASD). Abnormalities in glial cell development and proliferation and increased glial cell apoptosis contribute to the adverse effects of ethanol on the developing brain and it is becoming apparent that the effects of fetal alcohol are due, at least in part, to effects on glial cells affecting their ability to modulate neuronal development and function. The three major classes of glial cells, astrocytes, oligodendrocytes, and microglia as well as their precursors are affected by ethanol during brain development. Alterations in glial cell functions by ethanol dramatically affect neuronal development, survival, and function and ultimately impair the development of the proper brain architecture and connectivity. For instance, ethanol inhibits astrocyte-mediated neuritogenesis and oligodendrocyte development, survival and myelination; furthermore, ethanol induces microglia activation and oxidative stress leading to the exacerbation of ethanol-induced neuronal cell death. This review article describes the most significant recent findings pertaining the effects of ethanol on glial cells and their significance in the pathophysiology of FASD and other neurodevelopmental disorders.

Pattern of Retinal Nerve Fiber Layer Thickness Loss in Fetal Alcohol Syndrome: A Spectral-Domain Optical Coherence Tomography Analysis

“…Recent animal studies have implicated alcohol interference with the Sonic hedgehog pathway 1 and with glia cells ability to modulate neural development and function. 12 Alcohol inhibits astrocyte-mediated neuritogenesis and oligodendrocyte development, survival and myelination and activates microglia cells increasing oxidative stress and alcohol induced neuronal apoptosis. 12 These findings corroborate previous animal studies, which found loss of retinal ganglion cells and optic axons, delayed gliogenesis and myelination and a smaller optic nerve cross sectionalarea and retinal thickness as a result in FAS models.…”

“…12 Alcohol inhibits astrocyte-mediated neuritogenesis and oligodendrocyte development, survival and myelination and activates microglia cells increasing oxidative stress and alcohol induced neuronal apoptosis. 12 These findings corroborate previous animal studies, which found loss of retinal ganglion cells and optic axons, delayed gliogenesis and myelination and a smaller optic nerve cross sectionalarea and retinal thickness as a result in FAS models. [13][14][15][16] The diagnosis of optic disc hypoplasia can be difficult because the optic disc can be only slightly reduced in size.…”

Effects of postnatal alcohol exposure on hippocampal gene expression and learning in adult mice

“…Thus, alcohol may induce cognitive deficits not only by affecting individual genes but also by a process involving elements from the level of dendritic spine formation to adult stem cell division and migration (Guizzetti et al, 2014).…”

21st Century Research in Child Neurology

“…The interplay between these environmental factors and genetic factors, probably through epigenetic mechanisms, is probably crucial during brain development, leading to altered programs of neuronal differentiation and connectivity (Hagberg et al, 2015;Boivin et al, 2015). A growing concept is that glial cells (astrocytes, oligodendrocytes, and microglia) play an important role in many if not all these disorders (van Tilborg et al, 2016;Guizzetti et al, 2014). Another important concept is the window of selective vulnerability of various cell types during ontogenic events that leads to particular patterns of injury in preterm and term newborns (Ferriero and Miller, 2010).…”