Alcohol-Induced Effects in the Developing CNS - Glial Cells and Myelin

Phillips, Dwight

Abstract

The exposure of the human fetus to alcohol during gestation has been recognized as a problem of considerable clinical concern since the mid- '70's. 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 found in light microscopic studies of both humans nad 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 exposures 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 37.5% 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 artificially 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, spinal cord, cerebral, and cerebellar tissues will be removed and prepared for electron microscopy. Optic nerve tissue will be studied to determine and maturation and the results will be compared with previous studies using only postnatal exposures. Spinal cord tissue will be examined to study neuronal maturation and glial development in a more typical CNS area ant to verify any optic nerve findings. Cerebral and/or cerebellar tissues will be examined to study how the effects of alcohol on glial cell maturation may affect neuronal migration and maturation.