[Studies on monoamine metabolism in the rat brain with overdosage of manganese].

I studied the neuropsychiatric disorders occurring after overdose with manganese (Mn), which have been shown to be neurologically similar to Parkinson's disease. MnCl2 doses of 10 mg Mn/kg, administered a total of 15 times, were injected intraperitoneally into rats. Then I determined the concentration of monoamines, their metabolites and the activity of catecholamine-related enzymes of the rat brain using high-performance liquid chromatography (HPLC). 1) In the Mn-loaded rats, the concentration of dopamine (DA) was significantly decreased in the nucleus caudatus-putamen (C/P)(p less than 0.05), the thalamus (p less than 0.05) and in the mesencephalon (ME) (p less than 0.001), while that of homovanillic acid decreased in the C/P (p less than 0.05). The concentration of norepinephrine (NE) was decreased in the hypothalamus (p less than 0.01) and that of 3-methoxy-4-hydroxyphenyl-glycol was decreased in the C/P (p less than 0.001) and in the thalamus (less than 0.05); however serotonin and 5-hydroxyindoleacetic acid concentrations showed no variation from those of the controls. 2) As for the enzymes of catecholamine biosynthesis, tyrosine hydroxylase (TyrOHase) activity was increased in the hypothalamus (p less than 0.05) and was reduced in the ME (p less than 0.01). Dopa decarboxylase activity showed no change. Dopamine-beta-hydroxylase (DBH) activity was reduced in the C/P and the thalamus (p less than 0.05 respectively). Phenylethanolamine-N-methyltransferase activity was detected in the hypothalamus, the ME, and at low levels in the thalamus (p less than 0.01). Among the enzymes of catecholamine metabolism, catechol-O-methyltransferase activity showed no variation, but monoamine oxidase (MAO) type-a and type-a + b activities were significantly increased in the cerebral cortex (p less than 0.01), and MAO type-a + b as significantly reduced in the C/P and the hypothalamus (p less than 0.01). The decrease on DA and NE contents found could be due to the reduction of such biosynthesizing enzymes as TyrOHase and DBH. Especially, the DA content was markedly decreased in the ME, found mostly in regions where DA neurons originate. Thus the variation of this region would be the first disorder. And it was interesting to note that MAO type-a + b was reduced by Mn administration.