Ethanol Exposure During Brain Development Alters Astrogliogenesis and Astrocyte Functions

Abstract

One of the most severe consequences of maternal alcohol consumption during pregnancy is the damage to the developing central nervous system (CNS) which is manifested by mental retardation and other CNS dysfunctions. The extreme consequence of these effects is the fetal alcohol syndrome (FAS). Alterations in neuronal migration have been proposed as a mechanism involved in alcohol-induced CNS damage. Since astroglial cells are responsible for the guidance of migrating neuronal bodies, promotion of neurite outgrowth, and shaping of neuronal assemblies during development, we have postulated that alcohol-induced alterations of astroglial functions could be important in contributing to the effect of ethanol on the developing brain. Using an animal model which reproduces in the rat many of the alterations observed in children with FAS, we have demonstrated, both in vivo and in vitro (astrocytes in primary cultures), that prenatal alcohol exposure induces important alterations in the astrogliogenesis. In fact, several groups including ours have demonstrated that alcohol induces decreases in either DNA synthesis or cell proliferation, decreases in protein synthesis and content, decreases in serotonin uptake, alterations in cytoskeleton organization and in the acquisition of several cytoskeletal proteins, delays in morphological maturation, increases in oxidative stress and alterations in neurotrophins. The main conclusion which can be drawn from these results is that the effects of prenatal expsoure to alcohol on astrocytes could significantly contribute to ethanol-associated alterations in CNS development.