PURKINJE-CELL DEFICITS IN NONHUMAN-PRIMATES FOLLOWING WEEKLY EXPOSURETO ETHANOL DURING GESTATION

The most serious features of fetal alcohol syndrome (FAS) are mental r etardation and other behavioral problems resulting from alcohol-induce d damage to the developing central nervous system (CNS). The mechanism by which alcohol induces its neuroteratogenic effects is unknown. One hypothesis is that gestational alcohol exposure results in a reductio n in neuronal number. This study demonstrates that gestational exposur e to ethanol in a non-human primate species induces permanent dose-rel ated deficits in the number of cerebellar Purkinje cells. Ethanol was administered via nasogastric tube once per week to 15 gravid pigtailed macaques (Macaca nemistrina) in one of the following doses: 0.0 (intu bated controls), 1.2, 1.8, 2.5, 3.3, and 4.1 g/kg/dose. Offspring were reared with parental surrogates and were sacrificed at 6 months of ag e; 8-mu m-thick parasagittal sections were cut through the paraffin-em bedded cerebellar vermis. Purkinje cells were quantified, the length o f the Purkinje cell line was determined stereologically, and Purkinje cell linear frequency was calculated. The number of Purkinje cells and their linear frequencies were significantly reduced in the alcohol-tr eated subjects, and the deficits were dose-dependent. The groups recei ving 2.5 g/kg/dose and above were most severely affected and had an av erage deficit in Purkinje cell number of 11.8%, relative to controls. Alcohol had no effect on the length of the Purkinje cell line. The fin dings suggest that alcohol-induced reduction in neuronal number may be an important factor underlying the CNS dysfunction in FAS. (C) 1996 W iley-Liss, Inc.