Prenatal Ethanol Exposure and Postnatal Environmental Intervention Alter Dopaminergic Neuron and Microglia Morphology in the Ventral Tegmental Area During Adulthood.

Abstract

BACKGROUND\nPrenatal ethanol exposure (PE) impairs midbrain dopaminergic (DA) neuron function, which might contribute to various cognitive and behavioral deficits, including attention deficits and increased addiction risk, often observed in individuals with fetal alcohol spectrum disorders (FASD). Currently, the underlying mechanisms for PE-induced deficits are unclear. Prenatal ethanol exposure could lead to neuroinflammation by activating microglia, which play an important role in synaptic function. In the present study, we investigated PE effects on microglial activation and DA neuron density and morphology in the ventral tegmental area (VTA). Since postnatal environmental enrichment can reduce neuroinflammation and ameliorate several PE-induced behavioral deficits, we examined if a postnatal environmental intervention strategy using neonatal handling and post-weaning complex housing could reverse PE effects on VTA DA neurons and microglia.\n\n\nMETHODS\nPregnant rats received 0 or 6\xa0g/kg/day ethanol by two intragastric intubations on gestation days 8 - 20. After birth, rats were reared in the standard laboratory or enriched condition. Male adult rats (8-12\xa0weeks old) were used for immunocytochemistry.\n\n\nRESULTS\nThe results showed that PE decreased VTA DA neuron body size in standardly housed rats. Moreover, there was a significant decrease in numbers of VTA microglial branches and junctions in PE rats, suggesting morphological activation of microglia and possible neuroinflammation. The PE effects on microglia were normalized by postnatal environmental intervention, which also decreased the numbers of microglial branches and junctions in control animals, possibly via reduced stress.\n\n\nCONCLUSIONS\nOur findings show an association between PE-induced morphological activation of microglia and impaired DA neuron morphology in the VTA. Importantly, postnatal environmental intervention rescues possible PE-induced microglial activation. These data support that environmental intervention can be effective in ameliorating cognitive and behavioral deficits associated with VTA DA neuron dysfunctions, such as attention deficits and increased addiction risk.