Long-lasting reduction in hippocampal neurogenesis by alcohol consumption in adolescent nonhuman primates

Abstract

Binge alcohol consumption in adolescents is increasing, and studies in animal models show that adolescence is a period of high vulnerability to brain insults. The purpose of the present study was to determine the deleterious effects of binge alcohol on hippocampal neurogenesis in adolescent nonhuman primates. Heavy binge alcohol consumption over 11 mo dramatically and persistently decreased hippocampal proliferation and neurogenesis. Combinatorial analysis revealed distinct, actively dividing hippocampal neural progenitor cell types in the subgranular zone of the dentate gyrus that were in transition from stem-like radial glia-like cells (type 1) to immature transiently amplifying neuroblasts (type 2a, type 2b, and type 3), suggesting the evolutionary conservation of milestones of neuronal development in macaque monkeys. Alcohol significantly decreased the number of actively dividing type 1, 2a, and 2b cell types without significantly altering the early neuronal type 3 cells, suggesting that alcohol interferes with the division and migration of hippocampal preneuronal progenitors. Furthermore, the lasting alcohol-induced reduction in hippocampal neurogenesis paralleled an increase in neural degeneration mediated by nonapoptotic pathways. Altogether, these results demonstrate that the hippocampal neurogenic niche during adolescence is highly vulnerable to alcohol and that alcohol decreases neuronal turnover in adolescent nonhuman primate hippocampus by altering the ongoing process of neuronal development. This lasting effect, observed 2 mo after alcohol discontinuation, may underlie the deficits in hippocampus-associated cognitive tasks that are observed in alcoholics.self-administration | binge drinking | hippocampal stem cells | neuronal development | cell death

Ethane-β-Sultam Modifies the Activation of the Innate Immune System Induced by Intermittent Ethanol Administration in Female Adolescent Rats

“…In another study of marque monkeys, where a binge type regime was administered for varying time periods, there were significantly decreased numbers of actively dividing type 1, 2a, and 2b cell types without significantly altering the early neuronal type 3 cells. Such results, as concluded by the authors, were caused by alcohol interfering with the division and migration of hippocampal pre-neuronal progenitors [44].…”

Adult Neurogenesis and Psychiatric Disorders

“…In mice, long-term voluntary alcohol self-administration for 10 weeks in a twobottle free-choice test enhanced proliferation in the dentate gyrus, with new cells surviving and differentiating normally (Aberg et al 2005). Chronic alcohol treatment over 11 months in adolescent macaque monkeys, on the other hand, resulted in long-lasting reduction in number of proliferating neural stem cells in dentate gyrus (Taffe et al 2010). Moreover, in the abstinence state following withdrawal from chronic alcohol consumption, depressive-like behavior and reduced numbers of neural progenitors and immature neurons were observed in the dentate gyrus of adult mice and both structural and behavioral phenotypes are alleviated by the antidepressant desipramine (Stevenson et al 2009).…”

A Molecular Mechanism of Ethanol Dependence: The Influence of the Ionotropic Glutamate Receptor Activated by N-Methyl-D-Aspartate

“…Alcohol significantly reduced the number of different neural progenitor cell types 1, 2a, and 2b as well as glial progenitor cells (Taffe et al, 2010). This suggests that alcohol interferes with the division and migration of progenitor cells in the hippocampus preneuronal region.…”

“…This effect diminishes slowly and can be seen two months after alcohol abstinence. These findings could explain the deficit in the hippocampus associated with cognitive tasks that may be associated with increased DNA binding of NF-kB and reduced DNA binding of CREB (Fulton et al, 2009, Taffe et al, 2010.…”