Consequences of adolescent alcohol use on adult hippocampal neurogenesis and hippocampal integrity

Abstract

Alcohol is the most commonly used drug among adolescents. Their decreased sensitivity to self-regulating cues to stop drinking coincides with an enhanced vulnerability to negative outcomes of excessive drinking. In adolescents, the hippocampus is one brain region that is particularly susceptible to alcohol-induced neurodegeneration. While cell death is causal, alcohol effects on adult neurogenesis also impact hippocampal structure and function. This review describes what little is known about adolescent-specific effects of alcohol on adult neurogenesis and its relationship to hippocampal integrity. For example, alcohol intoxication inhibits neurogenesis persistently in adolescents but produces aberrant neurogenesis after alcohol dependence. Little is known, however, about the role of adolescent-born neurons in hippocampal integrity or the mechanisms of these effects. Understanding the role of neurogenesis in adolescent alcohol use and misuse is critical to our understanding of adolescent susceptibility to alcohol pathology and increased likelihood of developing alcohol problems in adulthood.

Keywords: Adolescence; Alcohol; Alcoholism; Ethanol; Hippocampus; Neural stem cell; Neurogenesis.

Figure 1:

In the rodent brain adult neurogenesis occurs in at least two regions, one of which is the hippocampus. (A) As part of normal brain functioning, new neurons are born in the subgranular zone of the dentate gyrus of the hippocampus. (B) In adolescent rats, reactive neurogenesis following ethanol administration leads to increased abnormal “ectopic” migration of newborn neurons. (C) Adult neurogenesis is a multi-step process that occurs over a time-span of several weeks. First, neural stem cells proliferate and differentiate into neural progenitor cells, which themselves can proliferate and differentiate into neuroblasts. Some neuroblasts will gradually mature into adult neurons and migrate into the dentate gyrus granule cell layer. As newborn cells mature, they extend their axons to the CA3 pyramidal cells of the hippocampus, while their dendrites elongate and ramify to receive inputs from the entorhinal cortex. Alcohol can potentially affect any one or multiple steps in its overall effect on adult neurogenesis.