Date of Award:

5-1986

Document Type:

Thesis

Degree Name:

Doctor of Philosophy (PhD)

Department:

Animal, Dairy, and Veterinary Sciences

Department name when degree awarded

Toxicology

Committee Chair(s)

Raghubir P. Sharma

Committee

Raghubir P. Sharma

Committee

William Brindley

Committee

Reed Warren

Committee

David Drown

Committee

James A. Gessaman

Abstract

Neurochemical and immunological effects of manganese chloride (MnCl2) were evaluated using young male CD-1 mice as the animal model. Intraperitoneal (i.p.) injection of MnCl2 (1, 3 and 10 mg/kg) daily for 4 weeks did not produce mortality or overt signs of toxicity in any of the treated animals. Manganese treatment increased the thymidine uptake of cultured splenic cells and the selective lymphoproliferative response to T-cell mitogens, phytohaemagglutinin and concanavalin A, in all the treated groups. No difference in the response to B-cell mitogen, lipopolysaccharide was observed. A dose of 10 mg/kg MnCl2 increased the mixed lymphocyte response to allogeneic cells (Yac-1). Natural killer cell activity was not altered by manganese treatment. The immunological roles of manganese in male CD-1 mice were further evidenced by the dose-dependent immunosuppressive effects of MnCl2 on the development of antibody forming cells and the production of the antibody titre against sheep red blood cells. This suppressive effect of manganese was apparently reversible, as the number of plaque-forming cells and the anti-sheep red blood cell antibody titre in the 10 mg/kg MnCl2 treatment group recovered to levels comparable to the controls after manganese treatment had been halted for 2 weeks.

Subchronic manganese treatment (20 mg/kg, i.p. daily for 2 weeks) elevated the steady state levels and the turnover rates of dopamine (DA) in the corpus striatum. The endogenous content of serotonin (5-HT) increased in the cerebellum, whereas 5-hydroxyindoleacetic acid (5-HIAA) increased in the midbrain. After 4 weeks of exposure, manganese treatment had more selective effects on the major metabolites, 5-HIAA and 3,4-dihydroxyphenylacetic acid (DOPAC), than their parent compounds. A dose of 10 mg/kg MnCl2 reduced 5-HIAA levels in the cerebral cortex and medulla oblongata, whereas 1 mg/kg MnCl2 induced an opposite effect in the cerebral cortex. Increases in endogenous contents of DOPAC were also observed in both medulla oblongata and cerebellum. Levels as well as the specific receptor bindings of DA, norepinephrine (NE), and 5-HT were unaltered by MnCl2 treatment (1-10 mg/kg) after 4 weeks of exposure. Contrary to the in vivo results, an optimum concentration of manganese enhanced the specific bindings of dopamine-2, serotonin-2 and alpha-2 in the in vitro study.

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