Exposure to ethanol during brain development can permanently alter cerebellar and cerebral morphology and produce functional impairments in many aspects of behavior, including cognitive and motor performance. There currently is no known effective rehabilitation treatment for fetal alcohol syndrome (FAS). The long term objectives of this competing renewal are to identify methods to stimulate neuroplasticity that promotes rehabilitation of functional deficits resulting from brain damage induced by prenatal alcohol exposure. The general hypothesis is that complex motor learning, involving intensive training on an obstacle course, promotes structural neuroplasticity and ameliorates functional deficits in rats with brain damage induced by neonatal binge alcohol exposure. This period of brain development, comparable to that of the human 3rd trimester, is a time of heightened vulnerability to alcohol-induced cerebellar damage. Complex motor training in adulthood stimulated synaptic morphological plasticity of parallel fiber synapses in the cerebellar paramedian lobule (PML) and in motor cortex, and concurrently rehabilitated motor performance deficits. The three new aims build on this positive evidence of therapeutic rehabilitation, and now use early intervention initiated just after weaning.
Aim 1 will identify other structural correlates of the rehabilitative effects in PML and motor cortex, including evaluation of plasticity of climbing fibers and effects on astrocytes and vasculature.
Aim 2 will test whether the training can stimulate synaptogenesis in other regions of the cerebellum and in the hippocampus, and concurrently rehabilitate deficits in cerebellar-dependent and hippocampal dependent learning.
Aim 3 will determine whether rats with alcohol- induced brain damage have the capacity for neurogenesis in the postweaning or adult brain, and whether stimulation of adult neurogenesis (or enhanced survival of newly-generated neurons) by behavioral experience, has merit as a potential mode of rehabilitation. These studies will provide important new data that can guide and inform efforts to develop a rational approach to rehabilitation for children with FAS
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