Resistance of Postnatal Hippocampal Neurogenesis to Alcohol Toxicity in a Third Trimester-Equivalent Mouse Model of...

The adult hippocampal dentate is comprised of both developmentally generated dentate granule cells (dDGCs) and adult-generated dentate granule cells (aDGCs), which play distinct roles in hippocampal information processing and network function. EtOH exposure throughout gestation in mouse impairs the neurogenic response to enriched environment (EE) in adulthood, although the basal rate of adult neurogenesis under standard housing (SH) is unaffected. Here, we tested whether the production and/or survival of either dDGCs or aDGCs are selectively impaired following exposure of mice to EtOH vapors during early postnatal development (human third trimester-equivalent), and whether this exposure paradigm leads to impairment of EE-mediated dentate neurogenesis in adulthood.

All experiments were performed using NestinCreER^T2 :tdTomato bitransgenic mice, which harbor a tamoxifen-inducible tdTomato (tdTom) reporter for indelible labeling of newborn hippocampal DGCs. We exposed all mice to EtOH vapor or room air (Control) for 4 h/d from postnatal day (PND) 3 through PND 15. This paradigm resulted in a mean daily postexposure blood EtOH concentration of ~160 mg/dl. One cohort of neonatal mice received a single injection of tamoxifen at PND 2 and was sacrificed at either PND 16 or PND 50 to assess the impact of EtOH exposure on the production and long-term survival of dDGCs born during the early postnatal period. A second cohort of mice received daily injections of tamoxifen at PND 35 to 39 to label aDGCs and was exposed to SH or EE for 6 weeks prior to sacrifice.

Early postnatal EtOH exposure had no statistically significant effect on the production or survival of tdTom⁺ dDGCs, as assessed at PND 16 or PND 50. Early postnatal EtOH exposure also had no effect on the number of tdTom+ aDGCs under SH conditions. Furthermore, early postnatal EtOH exposure had no significant impact on the adult neurogenic response to EE.

Both early postnatal dentate neurogenesis and adult dentate neurogenesis, as well as the adult neurogenic response to EE, are surprisingly resistant to early postnatal EtOH vapor exposure in mice.