Similar to the dentate gyrus, the initial suppression of SVZ neurogenesis was followed by a burst of proliferation 3 d into abstinence, accompanied by a corresponding peak of new neuron formation of a similar magnitude. Most importantly, the peaks of proliferation and neurogenesis in the SVZ were followed by trend-level reductions in the proliferation markers, and a robust decrease in the neurogenesis marker by the end of the 3-wk abstinence interval studied. This late phase decrease in neurogenesis was accompanied by reduced numbers of SOX2-expressing cells. There are only two plausible mechanisms to account for reduced neurogenesis that result from decreased progenitor cell proliferation : a loss of progenitor cells, or interference with their progression through the cell cycle. The closely correlated decrease in both BrdU-IR and Ki67-IR at day 21 is not consistent with cell-cycle effects. Against this background, the most parsimonious interpretation of the data is that forebrain SVZ neurogenesis is long-term impaired following prolonged alcohol dependence through a loss of SOX2-expressing progenitor cells. These data complement a recent study showing permanent impairments in cell proliferation in the prefrontal cortex in a model of alcohol dependence (Richardson et al. 2009), and provide a potential mechanism for this observation.
