The purpose of this study is to characterize and quantitate effects of ethanol treatment on neurons in the aging central nervous system. Previous data showed (1) that ethanol induced dendritic degeneration in cerebellar Purkinje cells (PC) that resulted in longer surviving dendritic segments, (2) that ethanol depressed the number of synapses on PC dendrites reversibly such that significantly more synapses were formed on surviving dendrites during an extended recovery period, and (3) that ethanol did not alter the number of granule cells (GC), the source of most afferents to PC. The latter result contrasted with data from studies of younger ethanol-treated rats. Preliminary data also suggested that ethanol induced hypertrophy of the smooth endoplasmic reticulum (SER), an organelle involved in regulation of intracellular calcium levels in PC. Experiments are proposed to confirm and to build on the above results. First, immunocytochemical labeling of reactive astroglia and microglia, accepted markers of neuronal damage, will be used to confirm the extent and distribution of the dendritic degeneration. Second, immunocytochemical labeling of GABA+ synapses will be used to determine whether the increased number of synapses following recovery signaled an increase in inhibitory input to PC. Third, systematic morphometric measurements of SER profiles in shafts and spines of terminal dendrites will be used to determine whether the SER in dendritic shafts, especially at branch points, was preferentially altered by exposure to ethanol. Finally, the discrepancy stemming from the absence of cell loss in our old F344 rat model will be studied further to determine whether GC in young and old F344 rats differ in vulnerability to ethanol or whether GC in F344 rats are less vulnerable than GC in other rat strains at all ages. Results from this study are expected to contribute to our understanding of relationships between aging processes, alcohol abuse, and brain damage. This information is expected to promote the development of pharmacological interventions that will contribute to the health of elderly individuals in need of pharmacological assistance during recovery from long term alcohol dependency.
