EFFECTS OF METHYLMERCURY EXPOSURE DURING THE 2ND STAGE OF RAPID POSTNATAL BRAIN GROWTH ON NEGATIVE GEOTAXIS AND ON DELTA-AMINOLEVULINATE DEHYDRATASE OF SUCKLING RATS

In the present study, we examined the effects of exposure to methyl me rcury (0, 2.3,4.6,6.9 and 9.2 mg/kg, daily for 5 consecutive days, sc) during the second stage of rapid postnatal brain development (g to 12 days of age) on the sulfhydryl-containing enzyme delta-aminolevulinat e dehydratase (ALA-D, E.C. 4.2.1.24) from brain, liver and kidney and on motor performance (latency to complete a negative geotaxis response ) of rats. ALA-D specific activity of 13-day old rats of both sexes (7 -12 per group) was reduced significantly in rats treated with 6.9 mg/k g and 9.2 mg/kg in brain (about 40%, P<0.05) and in liver (about 25%, P<0.05). Renal ALA-D specific activity was not affected by methylmercu ry treatment. The in vitro IC50 for inhibition of brain, liver and ren al ALA-D was 79.3, 81.8 and 39.1 muM, respectively. The latency to com plete the negative geotaxis response of 12-day old rats was increased by 6.9 (7.9 +/- 0.7 s, mean +/- SEM) and 9.2 mg/kg methylmercury (7.8 +/- 0.5 s) when compared with control rats (5.8 +/- 0.3 s), suggesting an impairment in motor performance of exposed rats. These results dem onstrate that exposure to relatively high doses of methylmercury durin g the second stage of brain development causes a significant reduction in brain and hepatic ALA-D. The absence of inhibition of ALA-D by low er doses may be related to the relatively low in vitro sensitivity of the enzyme to methylmercury. The possible involvement of ALA-D inhibit ion on the neurotoxicity of methylmercury deserves additional investig ation.