Mental retardation and abnormal central nervous system development are among the most devastating consequences of the fetal alcohol syndrome.
This research aims to determine the effect of ethanol exposure on the developing neurons of the rat hippocampus during a period in the rat (postnatal days 4 to 10) equivalent to the third trimester in the human. The hippocampus receives a muscarinic cholinergic projection from neurons in the medial septal nucleus and the nucleus of the diagonal band. These cholinergic neurons synapse on the pyramidal cells of the hippocampus proper and granule cells of the dentate gyrus. Stimulation of these muscarinic cholinergic receptors causes increases in cyclic GMP, a second messenger involved in synaptic transmission in the septo-hippocampal pathway. Experimental studies have shown that ethanol exposure during development damages or destroys hippocampal pyramidal neurons. In preliminary studies, rats were exposed to ethanol from postnatal day 4 to day 10, using an artificial rearing procedure. They were then cross- fostered to other mothers, reared normally, and raised to adulthood. Exposure to cyclic blood alcohol concentrations with high peaks resulted in the following: greater hippocampal cyclic GMP response to maximal muscarinic cholinergic stimulation; and larger dissociation constants and a greater number of hippocampal muscarinic cholinergic receptors. Thus the alterations in muscarinic cholinergic receptors and cyclic GMP levels observed in our preliminary studies are consistent with permanent damage to muscarinic cholinergic function in the hippocampal formation of adult rats exposed to ethanol during the postnatal period. We now propose to determine whether these changes are due to reductions in acetylcholine levels in the hippocampal formation. We also wish to learn which neuronal cell type of the hippocampal formation is more subject to damage during this period of development - the pyramidal neurons of the hippocampus proper or granule cells of the dentate gyrus. This research will help determine whether neurons exposed to ethanol during the period of their development are subject to greater damage than neurons born prior to exposure to ethanol.
| Black Jr, A C; Goolsby, L W; Cohen, G A et al. (1995) Effects of prenatal ethanol exposure on the hippocampal neurochemistry of albino rats at 90 days of postnatal age. Am J Obstet Gynecol 173:514-9 |
