The overall objective of this project is to obtain an understanding of the effect of ethanol-hormone interaction on the developing cerebellum. We propose experiments which are expected to provide answers to questions about the effect of ethanol on cell proliferation and migration in the cerebellum and the modulation of this response by hormones which are active during differentiation and development of the nervous system. The proposed studies will utilize light microscopic autoradiographic and biochemical methods at both qualitative and quantitative levels to examine the effect of ethanol on the timing, rate and duration of neurogenesis and neuronal migration. These studies will be followed by experiments in which the hormonal environment of the developing cerebellum will be altered by the administration of exogenous hormones or anti-hormonal agents and their effect on cell proliferation and migration will be determined. Finally, experiments will be performed in which we will combine the administration of exogeneous hormones and ethanol to determine the interaction between these agents as they affect cerebellar development through modifications in the generation and migration of cerebellar neurons. The frog tadpole will be the animal model used in these studies, for it is an animal whose development is known to be controlled by various hormones, and because it is a free-swimming embryo that readily allows manipulation of its hormonal environment. The experiments proposed in this project are unique in the study of ethanol-hormonal interaction during nervous system development and are eminently practical because of the use of this unusually well suited animal model in which alterations of hormonal environments in developing embryos can be performed readily in the intact animal, and without modification by placental barrier, maternal hormonal pool or maternal metabolic activity. Insights into modulations of the effect of ethanol on the developing nervous system through hormonal manipulations appears to be a reachable goal consequent to the proposed studies and will prove to be of considerable value in elucidating the mechanism of nervous system damage in the fetal alcohol syndrome.
