Ethanol-Induced Apoptotic Neurodegeneration and Fetal Alcohol Syndrome

TLDR

Ethanol’s harmful impact on the developing human brain is poorly understood, especially during the synaptogenesis period that spans from the sixth month of gestation to several years after birth. Ethanol induces widespread apoptotic neurodegeneration in the developing rat forebrain by blocking NMDA receptors and overactivating GABA(A) receptors, and transient exposure during synaptogenesis can delete millions of neurons, accounting for the reduced brain mass and neurobehavioral deficits seen in fetal alcohol syndrome.

Abstract

The deleterious effects of ethanol on the developing human brain are poorly understood. Here it is reported that ethanol, acting by a dual mechanism [blockade of N-methyl-D-aspartate (NMDA) glutamate receptors and excessive activation of GABA(A) receptors], triggers widespread apoptotic neurodegeneration in the developing rat forebrain. Vulnerability coincides with the period of synaptogenesis, which in humans extends from the sixth month of gestation to several years after birth. During this period, transient ethanol exposure can delete millions of neurons from the developing brain. This can explain the reduced brain mass and neurobehavioral disturbances associated with human fetal alcohol syndrome.