Neuroimmune and epigenetic mechanisms underlying persistent loss of hippocampal neurogenesis following adolescent intermittent ethanol exposure.

Alcohol abuse and binge drinking are common during adolescence - a maturational period characterized by heightened hippocampal neuroplasticity and neurogenesis. Preclinical rodent models of adolescent binge drinking (i.e., adolescent intermittent ethanol [AIE]) find unique vulnerability of adolescent hippocampal neurogenesis with reductions persisting into adulthood after ethanol cessation. Recent discoveries implicate increased neuroimmune signaling and decreased neurotrophic support through epigenetic mechanisms in the persistent AIE-induced loss of neurogenesis. Importantly, interventions aimed at rectifying the increased neuroimmune signaling and neurotrophic-epigenetic modifications through physical activity, anti-inflammatory drugs, and histone deacetylase inhibitors protect and recover the loss of neurogenesis and cognitive deficits. The mechanisms underlying the persistent AIE-induced loss of adult hippocampal neurogenesis could contribute to broader neurodegeneration, loss of hippocampal neuroplasticity, and cognitive dysfunction.