Corpus callosum and visual cortex of mice with deletion of the NMDA-NR1 receptor: II. Attenuation of prenatal alcohol exposure effects

Abstract

Offspring of transgenic mice with deletion of the NMDA-NR1 (NR1) receptor received prenatal alcohol exposure during most of gestation. Before and after birth, offspring were sacrificed in order to examine the morphological consequences of the prenatal exposure. Previously, we reported that the dendritic arborization of corpus callosum projection neurons (CCpn) in visual cortex was abnormal in rats given prenatal alcohol exposure; the effects were dose-dependent [Neurotoxicol. Teratol. 24 (2002) 719–732]. The same parameters were examined in the transgenic mice. Crystals of DiI were placed into the CC of mice at different ages that had been prenatally exposed to alcohol. Controls included untreated transgenic mice, and transgenic mice with the same nutritional and handling stressors. Compared to Controls, prenatal alcohol exposure caused the NR1+/+ mice to expand the dendritic arbor of CCpn in visual cortex. The dendritic arbors had increased branch numbers and length; these increases were dose-dependent. In contrast, the prenatally exposed NR1−/− mice showed normal dendritic arbors with all prenatal alcohol doses. In addition, prenatal alcohol exposure was found to have morbidity and teratogenic effects on offspring. In seven separate indicators of the effects of prenatal alcohol exposure, only one indicator was present but reduced in NR1−/− offspring, indicating that total deletion of the NMDA-NR1 receptor throughout development largely blocks but sometimes attenuates the effects of prenatal alcohol exposure. Similarly, in seven separate indicators of the effects of prenatal alcohol exposure, five indicators were attenuated in NR1+/− compared to NR1+/+ offspring, although affected more than in NR1−/−; this suggests a gene–dose effect. The results indicate that functional NMDA-NR1 receptors are necessary for the neurotoxic and teratogenic effects of prenatal alcohol exposure. This study will aid in understanding how the NMDA receptors play an important role in prenatal alcohol effects on brain development.