Varying degrees of central nervous system (CNS) dysfunction represent the most devastating effect in offspring that survive heavy fetal alcohol exposure. Structural defects in the developing brain are likely responsible for some of the altered behavior. One of the basic questions of fetal alcohol research is whether there are periods of development when alcohol exposure is particularly harmful to the brain. The purpose of the proposed research is to determine the effects of alcohol exposure on the hippocampal formation and cerebellum in the rat, during a period of brain development equivalent to the human third trimester. This will be accomplished by using an artificial rearing procedure to provide adequate nutrition to neonatal rats, while exposing them to alcohol. Specifically, the following questions related to third trimester alcohol exposure will be addressed: 1) What is the extent of alcohol-induced neuronal deficits in the hippocampal formation and cerebellum, and are such deficits related to the relative development (chronology) of the specific subregions of these structures? 2) Is the brain's microvascular system altered by such exposure, and if so, are the changes permanent? 3) Is the alcohol exposure cytotoxic to neurons throught the brain, and do other regions exhibit signs of dose-dependent vulnerability? 4) Does the altered CNS responsiveness, (lesion-induced axon sprouting) exhibited by rats exposed prenatally to alcohol, occur in rats exposed to alcohol during the third trimester period of brain development? These experiments extend and expand the research of the past two years; they represent the first attempt to generate quantitative microscopic data concerning fundamental questions from two different brain regions (i.e., the hippocampal formation and the cerebellum). Neuron counting, morphometric analysis, cell degeneration staining, and anterograde horseradish peroxidase (HRP) techniques will be used to quantify third trimester alcohol effects. The data gleaned from these experiments will provide important information concerning the relative vulnerability of different brain areas as a consequence of third trimester alcohol exposure. As such, they will be important in assessing the potential hazards of heavy maternal alcohol consumption late in pregnancy on the structural development of the brain of the human fetus.
