Mechanisms involved in central nervous system dysfunctions induced by prenatal ethanol exposure

Abstract

Clinical and experimental evidence has demonstrated that ethanol is a teratogen, and that its consumption during pregnancy induces harmful effects on the developing foetus that leads to foetal alcohol syndrome (FAS). Central nervous system dysfunctions are the most severe and permanent consequence of maternal alcohol intake and can occur in absence of gross morphological defects associated with FAS. Mental retardation and long-term cognitive and behavioural deficits are some of the problems commonly found in children of women who were moderate or heavy drinkers during pregnancy. Experimental evidence demonstrates that alcohol interferes with many molecular, neurochemical and cellular events occurring during the normal development of the brain. Some brain areas are more affected than others and, even within a given region, some cell populations are more vulnerable than others. The neocortex, hippocampus and cerebellum are especially susceptible to alcohol and have been associated with the behavioural deficits. For example, alcohol exposure during the development of neocortex increases natural apoptosis and induces cell necrosis. These effects may be associated with ethanol-induced alterations in both neurotrophic support, and the expression of cell adhesion molecules, which may affect cell-cell interactions and cell survival. Experimental evidence also shows that alcohol disrupts radial glial and astroglial development which may lead to alterations in cell migration and neuronal survival and differentiation. Impairment of several neurotransmitter systems and/or their receptors, as well as changes in the endocrine environment during brain development, are also important factors involved in the neurodevelopmental liabilities observed after in utero alcohol exposure.