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[Studies on monoamine metabolism in the rat brain with overdosage of manganese]
1Department of Legal Medicine, School of Medicine, Toho University, Tokyo, Japan.
Abstract:
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.
Insights
Manganese overdose in rats significantly reduced dopamine and norepinephrine levels, impacting brain regions crucial for motor control. These changes were linked to altered catecholamine-related enzyme activity, suggesting a potential mechanism for manganese-induced neurotoxicity.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Context:
- Manganese (Mn) exposure can lead to neuropsychiatric disorders with Parkinson's-like symptoms.
- Understanding the neurochemical effects of manganese overdose is crucial for diagnosing and treating related neurological conditions.
Purpose:
- To investigate the impact of manganese chloride (MnCl2) overdose on monoamine concentrations and catecholamine-related enzyme activity in rat brains.
- To identify specific brain regions and neurochemical pathways affected by manganese toxicity.
Summary:
- Rats injected with MnCl2 showed significant decreases in dopamine (DA) in the caudate-putamen (C/P), thalamus, and mesencephalon (ME), and norepinephrine (NE) in the hypothalamus.
- Enzyme activity alterations included increased tyrosine hydroxylase (TyrOHase) in the hypothalamus, reduced dopamine-beta-hydroxylase (DBH) in C/P and thalamus, and altered monoamine oxidase (MAO) activity in various brain regions.
- The observed decrease in DA and NE content may be attributed to reduced biosynthesis enzyme activity, with the mesencephalon showing the most significant DA reduction, potentially indicating the primary site of disorder.
Impact:
- This study highlights the neurochemical alterations in the brain following manganese overdose, providing insights into the mechanisms underlying manganese-induced neurotoxicity.
- Findings suggest that manganese-induced changes in catecholamine pathways could contribute to the development of Parkinson's-like symptoms.
- The research underscores the importance of monitoring manganese levels and understanding its effects on neurotransmitter systems.