PRENATAL EXPOSURE OF RATS TO AMMONIA IMPAIRS NMDA RECEPTOR FUNCTION AND AFFORDS DELAYED PROTECTION AGAINST AMMONIA TOXICITY AND GLUTAMATE NEUROTOXICITY

The aim of this work was to assess whether perinatal hyperammonemia im pairs the function of NMDA receptors and whether this impairment affor ds protection against acute ammonia toxicity and glutamate and NMDA ne urotoxicity. Rats were exposed to ammonia during the prenatal and lact ation periods by feeding the female rats an ammonium-containing diet s ince day 1 of pregnancy. After weaning (at postnatal day 21), the pups were fed a normal diet with no ammonia added. This treatment resulted in a marked decrease of the growth rate of the animals, which was mai ntained even 1 month after normalization of ammonia levels. Rats expos ed to ammonia were more resistant than controls to acute ammonia toxic ity 13 days after feeding a normal diet but not at 3 months. Primary c ultures of cerebellar neurons from hyperammonemic rats showed decrease d binding of [H-3]MK-801 and were remarkably more resistant than contr ols to glutamate and NMDA toxicities. Also, the increase in aspartate aminotransferase activity induced by low concentrations of NMDA was no t produced in such cultures. These results indicate that exposure to a mmonia during the prenatal and lactation periods results in long-lasti ng impairment of NMDA receptor function. This would be the reason for the delayed protection afforded by exposure to low ammonia levels agai nst acute ammonia toxicity in animals and against glutamate and NMDA t oxicity in neuronal cultures.