Purkinje cell deficits in nonhuman primates following weekly exposure to ethanol during gestation.
The most serious features of fetal alcohol syndrome (FAS) are mental retardation and other behavioral problems resulting from alcohol-induced 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 reduction in neuronal number. This study demonstrates that gestational exposure to ethanol in a non-human primate species induces permanent dose-related 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 (intubated 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 age; 8-microns-thick, parasagittal sections were cut through the paraffin-embedded cerebellar vermis. Purkinje cells were quantified, the length of 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-treated subjects, and the deficits were dose-dependent. The groups receiving 2.5 g/kg/dose and above were most severely affected and had an average deficit in Purkinje cell number of 11.8%, relative to controls. Alcohol had no effect on the length of the Purkinje cell line. The findings suggest that alcohol-induced reduction in neuronal number may be an important factor underlying the CNS dysfunction in FAS.
Bonthius
D J
DJ
Department of Pediatrics, University of Iowa College of Medicine, Iowa City, 52242, USA.
Bonthius
N E
NE
Napper
R M
RM
Astley
S J
SJ
Clarren
S K
SK
West
J R
JR
D000818:Animals; D004195:Disease Models, Animal; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology; D006801:Humans; D008254:Macaca nemestrina; D011689:Purkinje Cells / Q000187:drug effects*
D000431:Ethanol