A single day of alcohol exposure during the brain growth spurt induces brain weight restriction and cerebellar Purkinje cell loss

Abstract

The period of rapid brain growth that occurs relatively late in development has been shown to be vulnerable to alcohol-induced brain growth deficits and neuron loss in rats using repeated daily exposure to alcohol. This study examined whether a condensed exposure (binge) restricted to a single day during this period would be sufficient to restrict brain growth and produce neuron depletion. Using artificial rearing, alcohol was given to neonatal rats in two consecutive feedings on postnatal day 4, using a total dose of either 6.6 g/kg or 3.3 g/kg. The higher dose produced mean peak blood alcohol concentrations of 362 mg/dl, while the lower dose produced mean peak BACs of 153 mg/dl. The higher dose significantly restricted whole brain, forebrain, cerebellum and brain stem weights on postnatal day 10, with the cerebellum being most severely reduced. Cerebellar Purkinje cells, counted from a 2-μm section from the midsagittal vermis, were significantly reduced in the 6.6 g/kg group. Purkinje cell loss relative to controls was significant in most lobules (I–V, IX and X), but, notably, was not significant in the later maturing regions (lobules VI and VII). The 3.3 g/kg group had no significant reductions in regional brain weights. Although the overall number of Purkinje cells was nonsignificantly reduced relative to controls, the 3.3 g/kg dose did produce significant loss of Purkinje cells in lobule II. Exposure to high peak BACs, even for a relatively short period during the brain growth spurt, constitutes a substantial risk to the developing brain, and even a moderate exposure may result in loss of more vulnerable neurons. The pattern of cell death produced suggests that the maturational or metabolic state of Purkinje cells at the time of the alcohol insult may influence the vulnerability of these neurons to an alcohol insult.