title: Alcohol-induced Purkinje cell loss depends on developmental timing of alcohol exposure and correlates with motor performance.
abstract: Several reports indicate that neonatal ethanol exposure induces cerebellar Purkinje and granule cell loss if exposure occurs before postnatal day (PD) 7, and that cerebellar damage may underlie ethanol-induced motor deficits. The present study used an unbiased stereological method, the optical fractionator, to count total cerebellar Purkinje cell number in groups of Sprague-Dawley rats given binge-like ethanol exposure at different neonatal ages. Correlations between Purkinje cell number (of 55-day-old rats) and parallel bar motor performance (previously tested on PD 30-32) were also evaluated. One group was given binge-like exposure to 6.6 g/kg per day of ethanol via artificial rearing on PD 4 and 5 (PD 4/5); a second group on PD 8 and 9 (PD 8/9); and a third group on both PD 4 and 5 and 8 and 9 (Comb). Gastrostomy (CG) and suckle (SC) control groups were also included. Purkinje cells were significantly reduced in all three ethanol-treated groups compared to controls, but the severity of loss was significantly greater in the PD 4/5 and Comb groups (reduced by 42% and 45%, respectively, relative to GC) compared to the PD 8/9 group (reduced by 15%). Across treatment groups, the total cerebellar Purkinje cell number was significantly correlated with successful parallel bar traversal (r = +0.74), supporting the contention that ethanol-induced motor deficits may be associated with cerebellar cell loss. These data confirm the presence of windows of vulnerability of Purkinje cells to neurotoxic effects of binge ethanol treatment, and demonstrate that both the behavioral and neuroanatomical consequences of binge exposure depend on the developmental timing of the exposure.
authors.affiliation: Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037, USA. thomas3@mail.sdsu.edu
authors.forename: J D
authors.initials: JD
authors.lastname: Thomas
authors.forename: C R
authors.initials: CR
authors.lastname: Goodlett
authors.forename: J R
authors.initials: JR
authors.lastname: West
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D002452:Cell Count; D002492:Central Nervous System Depressants / Q000633:toxicity*; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000254:growth & development*; D000431:Ethanol / Q000633:toxicity*; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects*; D011689:Purkinje Cells / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol