Purkinje Cell Vulnerability to Developmental Ethanol Exposure in the Rat Cerebellum

Abstract

Ethanol exposure is a consistent and reliable producer of neuronal toxicity, especially during periods of enhanced neuronal vulnerability. For rat cerebellar Purkinje cells, the postnatal period during the time of the brain growth spurt exhibits the greatest vulnerability to ethanol. Analyses of studies completed over more than 20 years provides sufficient detail to allow for the determination of the specific vulnerable window for ethanol-induced loss of Purkinje cells. Data reporting Purkinje cell counts after ethanol exposure were compiled from 18 studies published since 1975. We conducted linear regression analysis between peak blood ethanol concentration (BEC) and percent reduction in Purkinje cells for the following individual postnatal (PN) days: PN4, PN5. PN6, PN7, and PN8 or beyond (+). The slope of the regression and the coefficients of determination (r2) were the primary factors of interest. Analysis of variance of the regressions was conducted to identify whether the slopes were significantly different from zero, or from each other. Exposures involving the PN4-6 period demonstrated the greatest significance in the relationship between BEC and reduction of Purkinje cell number. No significant differences were identified between different ethanol exposure techniques or for different Purkinje cell counting techniques. In addition, the initial day of exposure and the duration of exposure were not identified as critical variables. The literature database, developed over the past 20 years is clear in its direction that studies designed to identify the ethanol-specific mechanisms of Purkinje cell death are best designed to involve ethanol exposure during the vulnerable window of postnatal days 4-6.