Neuroanatomic and neurochemical abnormalities in nonhuman primate infants exposed to weekly doses of ethanol during gestation.
Ethanol was orally administered once per week to 54 gravid pigtailed macaques (Macaca nemestrina) in doses of 0.0, 0.3, 0.6, 1.2, 1.8, 2.5 or 4.1 gm/kg from the 1st week in gestation or in doses of 2.5, 3.3 or 4.1 gm/kg from the 5th week. Mean maternal peak plasma ethanol concentrations (MPPEC's) ranged from 24 +/- 6 mg/dl at the 0.3 g/kg dose to 549 +/- 71 mg/dl at the 4.1 g/kg dose. Thirty-three live born infants were assessed for abnormalities of physical and behavioral development. Ocular pathology, neuropathologic and neurochemical assessements were done on 31 animals at 6 months postnatal age. Microphthalmia was noted in three of the 26 animals exposed to ethanol. Retinal ganglion cell loss was significantly associated with intra-uterine ethanol exposure. Microphthalmia and retinal ganglion cell loss was observed in both the delayed and full-gestational exposed animals. No structural anomalies were found in the brains via gross inspection or light microscopy. Chemical abnormalities in the striatal nuclei were identified. Striatal dopamine concentrations increased with increasing MPPEC exposure (0-249 mg/dl) among animals exposed weekly to ethanol throughout gestation. Striatal dopamine concentrations decreased with increasing MPPEC exposure (260-540 mg/dl) among animals whose weekly exposure to ethanol was delayed until the 5th week of gestation. The same pattern of association was also noted between MPPEC and ultrastructural alterations in the caudate nucleus. The extent of ultrastructural alterations increased with increasing MPPEC among the full-gestational exposed animals and decreased with increasing MPPEC among the delayed-dose animals.
Clarren
S K
SK
Department of Pediatrics, University of Washington School of Medicine, Seattle 98195.
Astley
S J
SJ
Bowden
D M
DM
Lai
H
H
Milam
A H
AH
Rudeen
P K
PK
Shoemaker
W J
WJ
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D001921:Brain / Q000473:pathology*; D003342:Corpus Striatum / Q000473:pathology; D000431:Ethanol / Q000493:pharmacokinetics; D005123:Eye / Q000473:pathology; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology*; D008254:Macaca nemestrina; D008854:Microscopy, Electron; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011247:Pregnancy; D011954:Receptors, Dopamine / Q000187:drug effects; D019966:Substance-Related Disorders / Q000473:pathology*
D018377:Neurotransmitter Agents; D011954:Receptors, Dopamine; D015102:3,4-Dihydroxyphenylacetic Acid; D000431:Ethanol