Ethanol elevates fetal serum glutamate levels in the rat.
Glutamate is an important excitatory neurotransmitter. However, a sustained elevation of glutamate in the extracellular space may be toxic to neurons. Because the blood-brain barrier is incomplete in the developing fetus, an elevation of fetal serum glutamate could expose the immature, growing brain to potentially toxic levels of extracellular glutamate. Chronic ethanol consumption during pregnancy is associated with an increased risk for a complex array of congenital anomalies, including alterations in the CNS, a hallmark of the fetal alcohol syndrome. Some central nervous system changes appear to involve the glutamate receptor, including reduced number and altered function. One mechanism for receptor downregulation may be a sustained elevation in extracellular glutamate. We hypothesize that chronic ethanol exposure during pregnancy leads to an elevation in fetal serum glutamate. When rats were fed ethanol-containing liquid diet throughout pregnancy, growth retardation of fetuses was observed at sacrifice (gestation day 20). Within each group, ethanol-fed, pair-fed, and ad libitum chow-fed, serum glutamate levels were generally higher in the fetus than in the dam. Ethanol treatment had no effect on fetal or maternal serum glutamine, a reciprocal metabolite of glutamate. In contrast, ethanol treatment increased serum glutamate levels in the fetal serum by nearly 50%, compared with either of the control groups. Maternal serum glutamate was not affected. The finding of ethanol-induced elevation of fetal serum glutamate suggests that the developing brain might be concurrently exposed to elevated levels of extracellular glutamate. Chronic exposure to elevated glutamate during critical periods of brain development may contribute to the pathogenesis of the fetal alcohol syndrome.
Karl
P I
PI
Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, NY 11030, USA.
Kwun
R
R
Slonim
A
A
Fisher
S E
SE
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000503:physiopathology*; D005317:Fetal Growth Retardation / Q000503:physiopathology; D018698:Glutamic Acid / Q000097:blood*; D005973:Glutamine / Q000097:blood; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D017470:Receptors, Glutamate; D005973:Glutamine; D000431:Ethanol; D018698:Glutamic Acid