Date of Award


Degree Type


Degree Name

Doctor of Philosophy


Since manganese (Mn) is both an essential trace metal and, under conditions of excess exposure, a neurotoxic metal, it is important to reach a clearer understanding of how Mn is absorbed, distributed, accumulated, and excreted, as well as to determine the effects of Mn on various metabolic processes, particularly in the brain.;In the present series of studies, Mn was administered to rats via injection (ip or iv), or orally in drinking water.;Mn administered as a single iv dose was recovered primarily from the bile and liver, which together comprised about 80% of the recovered dose, 3 hrs after administration. Mn did not bind to presynthesized hepatic metallothionein. Although the simultaneous administration of Mn + L-dopa caused a significant decrease in the biliary excretion of Mn, no evidence was found to support the contention that the chelation of Mn by L-dopa is a significant factor influencing the distribution and excretion of either Mn or L-dopa.;In plasma, Mn binds extremely poorly to albumin compared to Cd, Zn, and Fe, but binds much better than Cd or Zn to transferrin. The binding of the Mn to plasma proteins is affected by pH, the valence state of Mn (Mn('2+) vs Mn('3+)), and species differences (human vs rat).;Mn increased in all tissues except liver due to daily ip injections of 3.0 or 3.5 mg Mn/kg for 30 days. Bone and pancreas revealed the largest increases. In blood, increased Mn levels were almost totally accounted for by increases in the erythrocyte fraction. In the brain, certain regions, such as the corpus striatum and midbrain tegmentum, accumulated higher than average levels of Mn compared to other brain regions. Increased Cu concentrations were detected in plasma, pancreas, duodenum, testes, bone, lung, and in several brain regions of the Mn-treated rats. Also, Zn levels in plasma and bone were significantly reduced, as were Mg levels in heart and bone. In the corpus striatum, no changes in the concentrations of any neurotransmitter (DA, NE, 5-HT), nor any of their metabolites (DOPAC, HVA, 5-HIAA) were observed, but in the frontal cortex and pons-medulla, DA levels were significantly elevated over control. There was no change in the concentrations of the DA metabolites, however, indicating that the synthesis of DA may be initially affected by subchronic Mn administration but not the rate of degradation. Levels of NE were also elevated in the pons-medulla of Mn-treated rats. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of author.) UMI



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