Manganese mineral interactions in brain

Manganese (Mn) is an essential mineral but is toxic when taken in excess. H owever, whether its interactions with other minerals in organs and cells ar e involved in mechanisms underlying Mn toxicity is poorly understood. We de signed a developmental rat model of chronic Mn treatment (Group A: 1 mg MnC l2. 4H(2)O per mi of drinking water; Group B: 10 mg MnCl2. 4H(2)O per mi of drinking water; Group C: 20 mg MnCl2. 4H(2)O per mi of drinking water; Con trol Group given water without manganese addition). Employing the model and instrumental neutron activation analysis, we investigated two hypotheses: (i) chronic manganese treatment alters the brain regional distribution of m anganese and this altered manganese distribution also leads to region-speci fic changes of other meta Is; (ii) chronic manganese treatment induces diff erential changes in subcellular distributions of metals and electrolytes. I n the treated rats, brain Mn level showed dose-related increases, the most pronounced being noted in striatum, hypothalamus, and hippocampus: these in creases also led to alterations in regional distribution pattern of Mn. In the treated rats, Fe level was increased in hypothalamus, cerebellum, hippo campus, pens and medulla, and striatum. CLI level was increased in pens and medulla, hippocampus, midbrain, and striatum. Se level was increased in ce rebellum, striatum, midbrain, hypothalamus, and pens and medulla. Zn level was increased in hypothalamus and striatum. Ca level was increased in midbr ain but decreased in cerebellum; however, Mg and Al levels were not markedl y affected, in brains of fn-treated rats, Mn levels in subcellular fraction s were all increased, being especially marked in nuclei, mitochondria, and synaptosomes; the subcellular distributions of Fe, Cu, Zn, and Mg were diff erentially altered although those of Al and Ca were minimally affected. The se results are consistent with our hypotheses and may have implications in manganese neurotoxicity. The cellular and molecular mechanisms underlying m anganese-mineral interactions in brain are still poorly defined and merit f urther investigation. (C) 1999 Inter Press, Inc.