Thus, the effects of alcohol on hippocampal NPC cell cycle phase distribution and kinetics were assessed in an adolescent rat model of an alcohol use disorder.
Cell cycle distribution was measured using a combination of markers (Ki-67, bromo-deoxy-uridine incorporation, and phospho-histone H3) to determine the proportion of NPCs within G1, S, and G2/M phases of the cell cycle. Cell cycle kinetics were calculated using a cumulative bromo-deoxy-uridine injection protocol to determine the effect of alcohol on cell cycle length and S-phase duration.
Binge alcohol exposure reduced the proportion of NPCs in S-phase, but had no effect on G1 or G2/M phases, indicating that alcohol specifically targets S-phase of the cell cycle.
Cell cycle kinetics studies revealed that alcohol reduced NPC cell cycle duration by 36% and shortened S-phase by 62%, suggesting that binge alcohol exposure accelerates progression through the cell cycle.
This effect would be expected to increase NPC proliferation, which was supported by a slight, but significant increase in the number of Sox-2+ NPCs residing in the hippocampal subgranular zone following binge alcohol exposure.
These studies suggest the mechanism of alcohol inhibition of neurogenesis but also reveal the earliest evidence of the compensatory neurogenesis reaction that has been observed a week after binge alcohol exposure.
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