Nuclear magnetic resonance study on the evaluation of energy metabolism in the brain in vivo-A case of rat brain intoxicated with methymercury-

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In spite of great efforts to elucidate the toxicity of organic mercury, the molecular and cellular mechanism of the toxicity remains still unclear. In the present study we focused on the effect of methylmercury on energy metabolism in brain, and conducted an NMR investigation aiming at evaluation of oxidative capacity in the brain in vivo. The following results have been obtained.1. A rat model of methylmercury poisoning was established by oral administration of 5mg Hg/kg body weight methylmercury daily for 12 days.2. A phosphorus-31 NMR measurements were successfully carried out to observe high energy phosphorus metabolites from the brain avoiding signal contamination from the surrounding muscles and skins by a combination of a surface coil probe and a surgical operation.3. In the methylmercury poisoned brain the steady state concentration of ATP was maintained normal, but that of phosphocreatine (PCr) was reduced to 4.78 mumolg^<-1> compared with the normal concentration of 5.48mumolg^<-1>.4. An ATP turnover rate both in the normal and poisoned brain was 0.22 mumolg^<-1> sec^<-1> from the ^<31>P NMR saturation transfer measurement.5. Oxidative phosphorylation capacity in in vivo brain was evaluated from the steady state PCr level and the ATP turnover rate assuming a Michaelis-Menten equation controlled by ADP on the oxidative phosphorylation reaction. The result demonstrated that the oxidative capacity in the poisoned brain was approximately 15% reduced compared with the normal brain.6. We are also developing a technique of proton localization spectroscopy for rat brain to observe metabolites which are not phosphorylated.