Prenatal exposure to methyl mercury in rats: Focus on changes in kynurenine pathway

Previous studies showed learning and memory deficits following prenatal exp osure to methyl mercury (MMC) in rats. Considering the described dysfunctio n in several neurotransmission systems after MMC exposure, one can surmise that changes in the kynurenine pathway could also be involved in an altered brain functional development. Thus we focused our attention on the potenti al alteration in the production of tryptophan metabolites by prenatal MMC e xposure. For this purpose, brains were removed, at postnatal days 21 and 60 , from rats treated, at gestational day 8, with saline or a single dose of MMC (8 mg/kg). The levels of tryptophan, glutamic, aspartic, kynurenic, ant hranilic, and quinolinic acids were determined in hippocampal tissues of bo th groups of rats. No change was detected in the concentration of aspartic, glutamic, and kynurenic acids in 21- and 60-day-old exposed rats in compar ison with age-matched controls. On the contrary, at 21 days of age but not at 60 days, we found a very significant reduction of anthranilic acid and, in parallel, an increase of quinolinic acid levels in MMC-exposed rats in c omparison with control animals. Finally in the same brain area, tryptophan levels were significantly increased both at 21 and 60 days of postnatal lif e. These results suggest that an imbalance in the kynurenine pathway could be involved in the toxic effects induced by MMC on brain development. (C) 2 001 Elsevier Science Inc.