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. One of the hallmark characteristics of the resultant fetal alcohol syndrome (FAS) is central nervous system (CNS) dysfunction, consequently there have been numerous experimental studies of the effects of alcohol on nerve cell development. However, the potential effects of alcohol on the development of CNS glial cells and their elaborations, have not been as well studied. We have previously shown, in an animal model of FAS, that developmental exposures to alcohol: delay the acquisition of myelin and the oligodendroglial cells that produce myelin; can cause a permanent reduction in myelin thickness; and, can cause an increase in the numbers and extent of astroglia (gliosis). In order to understand the cellular events involved in such alterations, there is a need to define the periods of occur at those times. This proposed project is a light microscopic immunocytochemical and electron animal model designed to specifically localized the temporal vulnerability and cellular events involved in the production of myelin disorders and gliosis due to developmental alcohol exposures. To produce such exposures, artificially reared rats will be provided gastrostomy fed diet containing high doses of alcohol during specific stages of postnatal development that correspond to times during the third trimester of human brain development. Control animals will include artificially reared animals without alcohol in their isocaloric diet and normal nursing rat pups. Other exposures, by adding controlled prenatal exposures with liquid diet to artificial rearing on days 1-10, will produce a full three trimester equivalency exposure. Optic nerve and spinal cord tissues will be removed and prepared for immunocytochemistry and electron microscopy from animals at 15 and 90 days of age. Optic nerve tissue will be studied to determine the specific effects of such an alcohol exposure on the development and maturation of glial cell lineages, myelin, and vascular limiting membranes. Spinal cord tissue will be examined to contrast two dorsal column nerve fiber tracts of differing origin and times of development (the corticospinal and general sensory tracts), as well as to verify optic nerve findings in a more typical CNS area.