Fetal ethanol exposure results in life-long and devastating effects on the nervous system. The most recognizable child with fetal alcohol syndrome (FAS) has growth retardation, craniofacial abnormalities and central nervous system (CNS) dysfunction, but represents only a portion of those children exposed to alcohol. For the affected individuals and their families the impact is immeasurable; the economic costs are difficult to estimate but significant. Central nervous system abnormalities may not be the entire basis for the motor deficits of the children including weakness and low muscle tone. Alcohol affects many systems in the developing nervous system and, understandably, most research on the effects of prenatal ethanol exposure is focused on the CNS. We know far less about fetal ethanol exposure and its effect on the peripheral nervous system (PNS), despite its importance in the maintenance of the body's internal milieu as well as in the function of the peripheral sensorimotor system. This system includes motor and sensory neurons, their glia (Schwann cells), peripheral nerves, neuromuscular junctions, and muscle cells. In an in vitro model of neuronal-glial interaction, we know that ethanol dramatically decreases Schwann cell numbers. Our hypothesis is that prenatal ethanol exposure alters the development and long term function of the PNS. While the Schwann cell may be a vulnerable target, the other PNS components may also be affected. The consequence is an abnormal neuromuscular system that contributes both to the motor deficits manifest by children with FAS and the persistent growth retardation. We have preliminary data that exposure of pregnant rats to ethanol results in reduced grip strength in female offspring. We specifically propose to develop and characterize an in vivo rat model that demonstrates an effect of fetal ethanol exposure on the PNS. Evidence of the effects of ethanol on the PNS will be monitored by testing grip strength in rats exposed to increasing concentrations of ethanol. Electrophysiological studies to record compound action potentials will test for abnormalities in the conduction properties of the sciatic nerve. We also propose preliminary experiments using immunocytochemical staining to investigate morphological correlates of the functional and physiological findings. We will focus on two components of the sciatic nerve, Schwann cells and axons. Our long term goal is to study the mechanism by which ethanol acts on the PNS, what components are adversely affected and what approaches may ameliorate these effects.
