Ethanol Alteration of the Neurogenic Niche Supplement

The public health goal of this project is to understand a mechanism of brain regrowth in abstinence from alcohol dependence. By understanding this process, we hope to discover novel treatment strategies (behavioral and pharmacological) for alcoholic brain damage and/or promote recovery from damage. In abstinence after alcohol dependence, a reactive burst in adult neurogenesis occurs in the hippocampus of rats exposed 4-days of binge alcohol. This burst results from an increase in neural stem cell (NSC) proliferation at 1 week (T168) following binge alcohol exposure (Nixon and Crews, 2004). The promotion of NSC proliferation and neurogenesis is driven by a milieu of factors within what is termed the neurogenic niche. Recent discoveries support that microglia contribute to this niche, and after damage, microglial activation may drive reactive neurogenesis (e.g. Ziv et al., 2006). Intriguingly, low levels or low gradations of microglia activation are associated with the secretion of neuroprotective agents such as growth factors and anti- inflammatory cytokines (Raivich et al., 1999). Thus, upon discovering a microglia event that suggests low-level activation (namely microglia proliferation), we suspected a causal link between microglial events and the promotion of neurogenesis during abstinence after alcohol dependence. Thus, the parent grant tests the hypothesis that binge alcohol exposure produces a graded microglial response that drives neural stem cell proliferation and subsequent neurogenesis observed in abstinence. This hypothesis is tested through three specific aims, the second of which is directed at examining the extent of microglial reactivity following binge ethanol exposure. This is the aim on which Alex Marshall has expressed interest in contributing.