ALCOHOL-INDUCED PURKINJE-CELL LOSS WITH A SINGLE BINGE EXPOSURE IN NEONATAL RATS - A STEREOLOGICAL STUDY OF TEMPORAL WINDOWS OF VULNERABILITY

Previous research has shown that the early neonatal period of rats is one of enhanced vulnerability to cerebellar Purkinje cell loss associa ted with binge-like alcohol exposure, with a prominent sensitive perio d during the first neonatal week. In this study, an unbiased count of the total number of Purkinje cells was obtained using the stereologica l optical fractionator, in groups of rats given a single hinge-like al cohol exposure either during the most vulnerable neonatal period [post natal day (PD) 4] or during a later, less vulnerable period (PD 9). Us ing artificial rearing methods, rats were given 6.6 g/kg of alcohol ei ther on PD 4 or can PD 9, delivered as a 15% (v/v) solution in milk fo rmula on two consecutive feedings of the designated day. Central group s included an artificially reared gastrostomy control and a normally r eared suckle control. The mean peak blood alcohol concentrations were no: different between the PD 4 and PB 9 alcohol groups, averaging 374 and 347 mg/dl, respectively. The rats were perfused on PD 27. A unifor m random sample of sections was obtained from serial frozen sections t hrough the cerebellum, stained with thionin, and Purkinje cells were c ounted from a uniform random sample of locations on each section with the three-dimensional optical fractionator. The number of Purkinje cel ls in the suckle control and gastrostomy control groups did not differ from each other, averaging 3.94 (+/-0.19) and 3.58 (+/-0.22) x 10(5) cells, respectively. Binge exposure on PD 4 induced significant cell l oss (mean of 2.05 +/- 0.20 x 10(5) Purkinje cells), whereas binge expo sure an PD 9 did not induce significant Purkinje cell lass (3.70 +/- 0 .39 x 10(5) Purkinje cells). These findings confirm that a single neon atal binge alcohol exposure produces pathological Purkinje cell loss, provided that it occurs during the period of enhanced vulnerability co inciding with the early stages of dendritic outgrowth.