Abstract
Alcohol is one of the most common noxious substance to which fetuses are exposed. The aim of the study was to determine the effects of in utero alcohol exposure on excitotoxin-induced neuronal migration disorders. Female hamsters received alcohol (7%) for 3–5 mo or for the last 9–12 d of gestation. Alcohol diet was continued for 5 d during lactation in both groups. Drinking behavior was monitored. Peak plasma alcohol levels were 104 ± 12 mg/dL and 225 ± 6 mg/dL after 30 min for hamsters receiving an intragastric dose of 3 mL or 5 mL alcohol, respectively. At birth, pups received intrapallial injections ibotenic acid (1 ng, 100 ng, or 10 μg). Histology and N-methyl-d-aspartic acid (NMDA) receptor labeling by 3H-MK-801 in the pups cortices were studied. Short-term-alcohol-exposed pups had normal body and brain weights at birth, but their body growth was retarded postnatally. Ibotenic acid induced similar neuronal migration impairments in control and alcohol-exposed pups (nodular heterotopia in the white matter and/or deep cortical layers, subpial ectopia, and micro- or polymicrogyria). The size of lesions induced by 100 ng ibotenic acid was increased in alcohol-exposed pups; the 10 μg dose was lethal. The density of 3H-MK-801 binding sites was similar in the three groups, indicating that exacerbated ibotenic acid excitotoxicity in alcohol-exposed pups did not result from increased NMDA receptor density. This study shows that alcohol exposure at levels that do not induce neuron migration disorders is sufficient to enhance the effects of the hypoxia-ischemia mimicking effects of ibotenic acid.
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Abbreviations
- ARND:
-
alcohol-related neurodevelopmental disorders
- FAS:
-
fetal alcohol syndrome
- GABA:
-
gamma-aminobutyric acid
- GFAP:
-
glial fibrillary acidic protein
- 3H-MK-801:
-
tritiated dizocilpine
- NeuN:
-
neuronal nuclear antigen
- NGF:
-
nerve growth factor
- NR2B:
-
NMDA receptor subunit encoded by the GRIN-2B gene
- NMDA:
-
N-methyl-d-aspartic acid
- PAF:
-
platelet-activating factor
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Acknowledgements
The authors thank Prof. Jean Costentin for allowing us to use the radio-imager and the drinking monitoring device, Dr. Jean François Ménard for his help in statistical analyses, M. Jean Paul Henry for his skillful handling of the animals, and Ms. Cathy Vendeville for her expert technical assistance.
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Supported by the Institut de Recherches scientifiques sur les Boissons (IREB), Paris, France, and the Région Haute-Normandie.
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Adde-Michel, C., Hennebert, O., Laudenbach, V. et al. Effect of Perinatal Alcohol Exposure on Ibotenic Acid-Induced Excitotoxic Cortical Lesions in Newborn Hamsters. Pediatr Res 57, 287–293 (2005). https://doi.org/10.1203/01.PDR.0000148712.30716.9D
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DOI: https://doi.org/10.1203/01.PDR.0000148712.30716.9D
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