Manganese mineral interactions in brain.

Manganese (Mn) is an essential mineral but is toxic when taken in excess. However, whether its interactions with other minerals in organs and cells are involved in mechanisms underlying Mn toxicity is poorly understood. We designed a developmental rat model of chronic Mn treatment (Group A: 1 mg MnCl2.4H2O per ml of drinking water; Group B: 10 mg MnCl2.4H2O per ml of drinking water; Group C: 20 mg MnCl2.4H2O per ml of drinking water; Control 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 manganese and this altered manganese distribution also leads to region-specific changes of other metals; (ii) chronic manganese treatment induces differential changes in subcellular distributions of metals and electrolytes. In the treated rats, brain Mn level showed dose-related increases, the most pronounced being noted in striatum, hypothalamus, and hippocampus: these increases also led to alterations in regional distribution pattern of Mn. In the treated rats, Fe level was increased in hypothalamus, cerebellum, hippocampus, pons and medulla, and striatum. Cu level was increased in pons and medulla, hippocampus, midbrain, and striatum. Se level was increased in cerebellum, striatum, midbrain, hypothalamus, and pons and medulla. Zn level was increased in hypothalamus and striatum. Ca level was increased in midbrain but decreased in cerebellum; however, Mg and Al levels were not markedly affected. In brains of Mn-treated rats, Mn levels in subcellular fractions were all increased, being especially marked in nuclei, mitochondria, and synaptosomes; the subcellular distributions of Fe, Cu, Zn, and Mg were differentially altered although those of Al and Ca were minimally affected. These results are consistent with our hypotheses and may have implications in manganese neurotoxicity. The cellular and molecular mechanisms underlying manganese-mineral interactions in brain are still poorly defined and merit further investigation.