EFFECTS OF ETHANOL EXPOSURE ON HYALURONAN-MEDIATED ADULT NEUROGENESIS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. There is growing evidence that cognitive impairments associated with alcoholism are linked in part to alterations in adult neurogenesis in the subgranular zone (SGZ) of the hippocampus. Ethanol administration can infuence the proliferation, survival and differentiation of neural progenitor cells that would otherwise differentiate into neurons that contribute to learning and memory. Our preliminary data indicate that neurogenesis in the SGZ is regulated in part by the glycosaminoglycan hyaluronan (HA) and its transmembrane receptor, CD44. Degradation of HA or disruption of CD44 results in aberrant SGZ-derived progenitor cell proliferation and aberrant neuronal differentiation. We found that transcripts for hyaluronidases, enzymes that degrade HA, are increased in the hippocampi of cynomolgus macaques that self-administer ethanol. These data suggest that alcohol administration promotes HA degradation and that this degradation contributes to aberrant neurogenesis and cognitive impairment. Here, we aim to: (1) Test the hypothesis that ethanol administration leads to altered HA synthesis and degradation in the adult non-human primate SGZ through a mechanism that involves increased transcription of hyaluronidase genes; and (2) Test the hypothesis that altered HA levels and distribution in the SGZs of non-human primates that self-administer ethanol correlate with alterations in neural progenitor cell proliferation and survival. This pilot study will provide new clues about how alcohol consumption influences adult neurogenesis.