The exposure of the human fetus to alcohol during gestation has been recognized as a problem of considerable clinical concern for the last dozen years. Although it is well recognized that one of the hallmark characteristics of the resultant fetal alcohol syndrome (FAS) is central nervous system (CNS) dysfunction, there have been relatively few ultrastructural studies of the cellular pathology in the CNS of experimentally exposed animals. Evidence of alcohol induced abnormal cellular differentiation and migration in the CNS have been fund in light microscopic studies of both humans and experimental animals and, in animals, potential abnormalities in myelin development have been noted. Because normal glial cell maturation is necessary for normal neuronal migration as well as myelin formation, it is of interest to examine developing glial cells and myelin, as well as nerve cells in experimental animals exposed to alcohol in a manner which will closely parallel the timing of exposure which occur in FAS. THis proposed project is an electron microscopic study of the development of glial cells, myelin, and later, nerve cells in the central nervous system of rats exposed to alcohol in such a model. To parallel the ethanol exposures of FAS, rats will be exposed for the 21 days of gestation via a maternal diet that contains 35% ethanol derived calories, then further exposed for 10 postnatal days by use of a milk diet containing 3% (v/v) ethanol. Postnatal animals will be artifically reared away from the mothers and the diet administered via chronically implanted gastric cannulas. Control animals will be raised from isocalorically pairfed dams, and fed via gastric cannulas, but without alcohol in the maternal or postnatal diet. Animals will be sacrificed at various times during gestation, during postnatal days, and up to maturity. Optic nerve and spinal cord tissues will be removed and prepared for electron microscopy. In the first portion of the study optic nerve tissue will be studied to determine if alcohol has an effect on gliogenesis and/or myelinogenesis. Further studies will determine if any effects on myelin and glial cells persist into maturity. In the last phase of the study the developing spiral cord from the same experimental animals will be examined to study neurogenesis and to verify any optic nerve findings in a more typical CNS area.
