Alcohol and the Developing Brain: Why Neurons Die and How Survivors Change

Abstract

The consequences of alcohol drinking during pregnancy are dramatic and usually referred to as fetal alcohol spectrum disorders (FASD). This condition is one of the main causes of intellectual disability in Western countries. The immature fetal brain exposed to ethanol undergoes massive neuron death. However, the same mechanisms leading to cell death can also be responsible for changes of developmental plasticity. As a consequence of such a maladaptive plasticity, the functional damage to central nervous system structures is amplified and leads to permanent sequelae. Here we review the literature dealing with experimental FASD, focusing on the alterations of the cerebral cortex. We propose that the reciprocal interaction between cell death and maladaptive plasticity represents the main pathogenetic mechanism of the alcohol-induced damage to the developing brain.

Keywords: GABA; apoptosis; cerebral cortex; ethanol; fetal alcohol; pyramidal neurons.

Figure 1

A schematic of the relationships between early alcohol exposure and cell death. Alcohol has immediate impacts upon the system which can lead to an increased apoptosis different from natural programmed cell death, yet also results in plastic changes to the brain. This can lead to a further imbalance of the system in terms of inhibition/excitation and cell excitability, creating a vicious cycle likely to result in further abnormal apoptosis. Critically, the impact of alcohol on all these factors is mediated by the duration of exposure, and the time of exposure in the developmental trajectory.