We explored the mechanism of alcohol inhibition of neurogenesis by systematically assessing the different components that contribute to the birth of new neurons. Several subtleties in the data reveal potential mechanisms of alcohol effects. First, alcohol inhibition of NSC proliferation in adolescent rats appears to be due to alcohol effects on cell cycle, and possibly cell cycle arrest. Proliferation is reduced by either altering the cell cycle or killing progenitor cells (Crews et al., 2003; Luo and Miller, 1998). Several pieces of these data suggest the former. For example, by the 4D+7 time point, DCX+IR had returned to control levels (Figure 2), which suggests that NSCs are not lost permanently. This interpretation is supported further by the Ki-67 data, which was not significantly different between the control and alcohol groups. As illustrated in Figure 8, Ki-67 and BrdU label different aspects of the cell cycle: Ki-67 is expressed during all active phases of the cell cycle (M G2, S and G1; Scholzen and Gerdes, 2000) whereas BrdU is incorporated into cells when the DNA is singled stranded, during the S-phase.
