英乙醇造成神经细胞凋亡的机理.doc

Mechanisms of Alcohol-Induced Damage to the Developing Nervous System Charles R. Goodlett, Ph. D. , and Kristin H. Horn CHARLES R. GOODLETT, PH. D. , is a professor in the Department of Psychology, Indiana University-Purdue University,Indianapolis, Indiana, and H. HORN is a Ph. D. candidate in Program in Medical Neurobiology, Indiana University School of Medicine, Indianapolis, Indiana. Numerous mechanisms likely contribute to the damaging effects of prenatal alcohol exposure on the developing fetus and particularly the developing central nervous system ( CNS) . The coexistence of a multitude of mechanisms that may act simultaneously or consecutively and differ among various cell types poses particular challenges to researchers. To study alcohol s effects on the fetus more easily, investigators have used animal models and tissue-culture experiments. Such approaches have identified numerous potential mechanisms through which alcohol acts on the fetus, many of which result in cell death by necrosis or apoptosis. Among these mechanisms are increased oxidative stress, damage to the mitochondria, interference with the activity of growth factors, effects on glia cells, impaired development and function of chemical messenger systems involved in neuronal communication, changes in the transport and uptake of the sugar glucose, effects on cell adhesion, and changes in the regulation of gene activity during development. KEY WORDS: prenatal alcohol exposure; central nervous system; oxidative stress; mitochondria; growth-arresting factors; embryologic development; alcohol-related intrauterine disorder; alcohol-related neurodevelopmental disorder; necrosis; neurotransmitters; glucose intolerance; cell adhesion molecules Maternal drinking during pregnancy can adversely affect the outcome of the offspring, with effects ranging from mild cognitive impairment, characterized by impaired mental activities, to full-blown fetal alcohol syndrome ( FAS) , characterized by growth defic