Neonatal Ethanol Disturbs the Normal Maturation of Parvalbumin Interneurons Surrounded by Subsets of Perineuronal Nets in the Cerebral Cortex: Partial Reversal by Lithium

Abstract

Reduction in parvalbumin-positive (PV⁺) interneurons is observed in adult mice exposed to ethanol at postnatal day 7 (P7), a late gestation fetal alcohol spectrum disorder model. To evaluate whether PV⁺ cells are lost, or PV expression is reduced, we quantified PV⁺ and associated perineuronal net (PNN)⁺ cell densities in barrel cortex. While PNN⁺ cell density was not reduced by P7 ethanol, PV cell density decreased by 25% at P90 with no decrease at P14. PNN⁺ cells in controls were virtually all PV⁺, whereas more than 20% lacked PV in ethanol-treated adult animals. P7 ethanol caused immediate apoptosis in 10% of GFP⁺ cells in G42 mice, which express GFP in a subset of PV⁺ cells, and GFP⁺ cell density decreased by 60% at P90 without reduction at P14. The ethanol effect on PV⁺ cell density was attenuated by lithium treatment at P7 or at P14–28. Thus, reduced PV⁺ cell density may be caused by disrupted cell maturation, in addition to acute apoptosis. This effect may be regionally specific: in the dentate gyrus, P7 ethanol reduced PV⁺ cell density by 70% at P14 and both PV⁺ and PNN⁺ cell densities by 50% at P90, and delayed lithium did not alleviate ethanol's effect.

http://ift.tt/2Hj5fpp