Dose-dependent effects of acute in vivo ethanol exposure on extracellular glutamate concentration in the cerebral cortex of the near-term fetal sheep.
The cerebral cortex is a target site of ethanol teratogenesis. L-Glutamate is a major excitatory neurotransmitter that plays an important neurotrophic role in brain development. It has been proposed that optimal function of the glutamate neuronal system is required for normal brain development; overactivation could lead to excitotoxic-induced neuronal injury, whereas underactivation could delay/restrict brain development. The objective of this study was to test the hypothesis that acute in vivo ethanol exposure alters basal glutamate release in the fetal cerebral cortex. The experimental approach involved measuring fetal cortical extracellular glutamate concentration using the technique of in vivo microdialysis. Near-term fetal sheep were chronically instrumented with a microdialysis probe placed in the parasagittal cortex. At 124 +/- 3 days of gestation, the effects of maternal intravenous infusion of 2 g or 4 g ethanol/kg maternal body weight or an equivalent volume of saline, given as four equally divided doses over 5 hr, on fetal cerebral cortical extracellular glutamate concentration were determined. None of the three treatment regimens produced fetal or maternal demise during the time course of the study. There was an ethanol dose-dependent increase, p = 0.005, in extracellular glutamate concentration in the fetal cerebral cortex. This increase was paroxysmal in nature and was not directly related to the fetal blood ethanol concentration. In view of the proposed role for glutamate in neuronal development, this apparent ethanol-induced increase in glutamate release may be important in the pathogenesis of ethanol teratogenesis involving the cerebral cortex.
Reynolds
J D
JD
Department of Anesthesia, University of Iowa College of Medicine, Iowa City 52242, USA.
Penning
D H
DH
Dexter
F
F
Atkins
B
B
Hrdy
J
J
Poduska
D
D
Chestnut
D H
DH
Brien
J F
JF
D000428:Alcohol Drinking / Q000009:adverse effects*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000493:pharmacokinetics; D005110:Extracellular Space / Q000187:drug effects*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000473:pathology*; D005865:Gestational Age; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D012756:Sheep
D000431:Ethanol; D018698:Glutamic Acid