MORPHOMETRIC EVIDENCE THAT THE TOTAL NUMBER OF SYNAPSES ON PURKINJE NEURONS OF OLD F344 RATS IS REDUCED AFTER LONG-TERM ETHANOL TREATMENT AND RESTORED TO CONTROL LEVELS AFTER RECOVERY

Clinical symptoms of alcohol abuse may be confused with symptoms of ag e-related neuropathologies in human patients. It is important, therefo re, to determine the relationships between alcohol abuse and changes i n brain structures in well-controlled studies of ageing subjects. Curr ently there is little well-documented information of this type availab le. The purpose of this study was to determine whether long-term ethan ol treatment during ageing would lead to reductions in synaptic input to cerebellar Purkinje neurons (PN) of old F344 rats that: (1) were mo re severe than those attributable to ageing alone; (2) might be respon sible for an ethanol-related deletion of dendritic segments of PN in o ld F344 rats shown previously in this laboratory. The total number of synapses per PN dendritic arbor was determined after ethanol treatment of old F344 rats for 40 weeks between 12 and 22 months of age and in similarly treated rats given a subsequent 20-week period of recovery b etween 22 and 27 months of age. Groups of age-matched rats fed a chow diet and water and rats pair-fed an isocaloric liquid diet lacking eth anol served as controls. The volume of the molecular layer per PN arbo r and the numerical density of synapses in the molecular layer was det ermined from light microscopic preparations of a fixed volume of the c erebellar cortex. Photographic montages of the ultrastructure of the m olecular layer of the cerebellum were also prepared from each rat for measurements of synaptic numerical densities. From the volume of the m olecular layer per PN arbor and the numerical density of synapses in t he molecular layer, the total number of synapses per PN arbor was esti mated for each rat. There was a significant reduction in synapses in t he old ethanol-treated rats relative to age-matched chow-fed rats. The re were also significant interactions between recovery and treatment p rior to recovery. During recovery, synaptic numbers in the old, ethano l-treated rats were restored to pre-recovery control levels whereas sy naptic numbers in the old, chow-fed rats were significantly reduced du ring the same period of time. There were no significant diet- or age-r elated changes in synaptic numbers in the pair-fed control rats during treatment or recovery. The pattern of reduction in synaptic numbers d uring ethanol treatment and restoration of synaptic numbers during rec overy from treatment paralleled the pattern of ethanol-related segment loss and recovery-related segment regrowth noted earlier in PN arbors of old F344 rats, suggesting that reductions in the numbers of synaps es and deletion of terminal dendritic segments were causally related i n this strain.