Ethanol neurobehavioral teratogenesis and the role of the hippocampal glutamate-N-methyl-D-aspartate receptor-nitric oxide synthase system.
The purpose of this review is to evaluate a proposed mechanism for ethanol neurobehavioral teratogenesis in the hippocampus, involving suppression of the glutamate-N-methyl-D-aspartate (NMDA) receptor-nitric oxide synthase (NOS) system. It is postulated that suppression of this signal transduction system in the fetus by chronic maternal consumption of ethanol plays a key role in hippocampal dysmorphology and dysfunction in postnatal life. This mechanism is evaluated critically based on the current literature and our research findings. In view of the apparent time course for loss of CA1 pyramidal cells in the hippocampus produced by chronic prenatal ethanol exposure that manifests in early postnatal life, it is proposed that therapeutic intervention, which targets the glutamate-NMDA receptor-NOS system, may prevent or lessen the magnitude of postnatal hippocampal dysfunction.
Kimura
K A
KA
Department of Pharmacology and Toxicology, Faculty of Health Sciences, Queen's University, K7L 3N6, Kingston, Ontario, Canada.
Reynolds
J N
JN
Brien
J F
JF
D000818:Animals; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011597:Psychomotor Performance / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism
D002492:Central Nervous System Depressants; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D019001:Nitric Oxide Synthase