Alcohol abuse is one of the leading causes of death in the United States. The debilitating effects of alcohol exposure are dramatically seen in children born to alcoholic women. Fetal Alcohol Syndrome consists of growth retardation and central nervous system dysfunction, and is one of the leading causes of mental retardation. The immunosuppressive effects of chronic alcohol use have been well documented. Similarly, recent evidence indicates that fetal alcohol exposure results in immunodeficiency in humans and animals. Whereas the immunosuppressive effects of ethanol on the immune system are under investigation, the effects of alcohol on the neuroimmune system have remained unexamined. In the CNS, astrocytes function as immunocompetent cells. Astrocyte cultures provide a simple model to examine the effect of ethanol on astrocyte proliferation and cytokine expression. In this application we show that exposure of cultured astrocytes to physiological relevant concentrations of ethanol markedly inhibit growth factor-induced astrocyte proliferation and cytokine expression. Further, growth factor-induced mitogenesis and cytokine expression were markedly inhibited in p astrocyte cultures prepared from rats exposed to alcohol prenatally, thus suggesting that prenatal alcohol exposure has deleterious effects on astrocyte progenitor cells. In this proposal we will rigorously test the hypothesis that alcohol functions as an immunosuppressive drug in the CNS though the inhibition of one, or more, of the primary components of the neuroimmune response. The goals of the proposed research are to first establish the cellular mechanisms through which ethanol exposure inhibits mitogenesis and cytokine expression in cultured astrocytes. Second, to determine if prenatal and postnatal alcohol exposure impairs a primary component of the neuroimmune response (i.e., astrogliosis) in an in vivo model of immune activation (i.e., wounding) in young and adult rats.
