The next two stages of hippocampal neural stem cell development, cell migration and differentiation, were visualized and quantified using the endogenous marker DCX. As previously shown with experimenter-delivered alcohol exposure paradigms (He et al., 2005), nondependent drinking and alcohol dependence decreased total DCX-IR cells. Additional morphological analysis in the present study assessed the specific affects of alcohol on DCX-IR cell types (early phase and late phase). Both nondependent and dependent conditions were associated with reductions in early-phase DCX-IR cells in the hippocampal SGZ. As such, alcohol exposure in the present study did not attenuate the number of late-phase DCX-IR cells, although chronic forced exposure to alcohol has been shown to impair dendritic outgrowth of late-phase DCX-IR cells (He et al., 2005), suggesting morphological marring of late-phase cells. Combining independent results from Ki-67 and DCX analysis, initial chronic alcohol exposure appeared to preferentially hinder the proliferation of hippocampal progenitors, and dependence-induced decreases in cell birth and not cell maturation may contribute to the neuronal loss seen in alcoholism.
