Effect of prenatal exposure to ethanol on glutamate and GABA immunoreactivity in macaque somatosensory and motor cortices: critical timing of exposure.

The present study explored the effects of gestational ethanol exposure on enduring changes in the distribution of projection neurons and local circuit neurons in somatosensory/motor cortex. Critical events in corticogenesis occur during macaque gestation: the first six weeks of gestation include the period of primary stem cell production and the next 18 weeks are marked by the birth, migration, early differentiation, and death of cortical neurons. Monkeys were exposed to ethanol (or saline) one day per week during the first six or during the entire 24 weeks of gestation. Offspring were killed as adolescents. Projection neurons and local circuit neurons were identified immunohistochemically with antibodies directed against glutamate and anti-GABA, respectively. In all animals, both projection neurons and local circuit neurons were distributed in all laminae of both somatosensory and motor cortices. Ethanol did not affect the size of Cresyl Violet-stained, glutamate-positive, or GABA-immunolabeled somata, however, it did decrease neuronal density. The total density of Cresyl Violet-stained neurons was reduced in monkeys treated with ethanol (or saline) one day per week during the first six weeks of gestation and during the entire 24 weeks of gestation. Similar reductions were detected for glutamate- and GABA-positive neurons. The densities of Cresyl Violet-stained and of glutamate- and GABA-expressing neurons were reduced in all cortical layers. The only exception was layer V which was unaffected in monkeys treated with ethanol (or saline) one day per week during the first six weeks of gestation and during the entire 24 weeks of gestation. Thus, the parallel effects on both neuronal subpopulations suggest that ethanol targets a population of undetermined neuronal precursors.