title: 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.
abstract: Clinical symptoms of alcohol abuse may be confused with symptoms of age-related neuropathologies in human patients. It is important, therefore, to determine the relationships between alcohol abuse and changes in brain structures in well-controlled studies of ageing subjects. Currently there is little well-documented information of this type available. The purpose of this study was to determine whether long-term ethanol treatment during ageing would lead to reductions in synaptic input to cerebellar Purkinje neurons (PN) of old F344 rats that: (1) were more severe than those attributable to ageing alone; (2) might be responsible for an ethanol-related deletion of dendritic segments of PN in old 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 between 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 ethanol served as controls. The volume of the molecular layer per PN arbor and the numerical density of synapses in the molecular layer was determined from light microscopic preparations of a fixed volume of the cerebellar cortex. Photographic montages of the ultrastructure of the molecular layer of the cerebellum were also prepared from each rat for measurements of synaptic numerical densities. From the volume of the molecular layer per PN arbor and the numerical density of synapses in the molecular layer, the total number of synapses per PN arbor was estimated for each rat. There was a significant reduction in synapses in the old ethanol-treated rats relative to age-matched chow-fed rats. There were also significant interactions between recovery and treatment prior to recovery. During recovery, synaptic numbers in the old, ethanol-treated rats were restored to pre-recovery control levels whereas synaptic numbers in the old, chow-fed rats were significantly reduced during the same period of time. There were no significant diet- or age-related changes in synaptic numbers in the pair-fed control rats during treatment or recovery. The pattern of reduction in synaptic numbers during ethanol treatment and restoration of synaptic numbers during recovery 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 synapses and deletion of terminal dendritic segments were causally related in this strain.
authors.affiliation: Department of Anatomy and Cell Biology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo 14214-3000, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Dlugos
authors.forename: R J
authors.initials: RJ
authors.lastname: Pentney
mesh_terms: D000367:Age Factors; D000430:Alcohol Withdrawal Delirium / Q000473:pathology; D000437:Alcoholism / Q000473:pathology*; D000818:Animals; D003712:Dendrites / Q000187:drug effects / Q000473:pathology; D000431:Ethanol / Q000633:toxicity*; D006801:Humans; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects; D011689:Purkinje Cells / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013569:Synapses / Q000187:drug effects*
chemical_list: D000431:Ethanol