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Striatal manganese accumulation induces changes in dopamine metabolism in the cirrhotic rat
S Montes1, M Alcaraz-Zubeldia, P Muriel
1Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía, Manuel Velasco Suarez DF., Mexico, Mexico.
Abstract:
Manganese (Mn) is an essential metal that, in excess, causes an extrapyramidal syndrome consisting in tremor, rigidity and akinesia. Recently, Mn was found to accumulate in brains of cirrhotic patients who also present motor abnormalities. Manganese alters dopaminergic transmission promoting an increase in the turnover of dopamine (DA). In this study, we studied the changes in dopamine and its main metabolite homovanillic acid (HVA) to evaluate DA turnover following administration of manganese to bile-duct obstructed rats. Some groups of rats were treated with manganese chloride in two concentrations: 0.5 and 1 mg/ml of Mn2+ in their drinking water. Four weeks after surgery and treatment with manganese, striatal Mn, DA and HVA were assessed. Marked increases (P<0.05) of striatal manganese content were observed in cirrhotic rats treated and untreated with manganese, these augments were dependent on the Mn concentration in water. Striatal contents of DA in cirrhotic rats diminished by 30% (P<0.05), administration of 0.5 mg/ml of manganese in drinking water to these rats returned dopamine to the basal level and 1 mg/ml of manganese increased dopamine content by 27%. The relationship of Mn content and DA turnover (HVA:DA) in the same animal showed a positive and statically significant correlation (P<0.05), with differences in slope for sham (b1=0.1528) and cirrhotic rats (b1=0.0174). These results suggest that manganese brain accumulation observed in liver failure could be a key element to understand dopamine metabolism in cirrhotic condition of humans.
Insights
Excess manganese accumulation in the brain, particularly in liver failure, significantly impacts dopamine levels and turnover. This study in cirrhotic rats reveals manganese
Area of Science:
- Neuroscience
- Biochemistry
- Toxicology
Background:
- Manganese (Mn) is essential but toxic in excess, causing neurological issues.
- Cirrhotic patients exhibit brain Mn accumulation and motor deficits.
- Manganese affects dopamine (DA) transmission and turnover.
Purpose of the Study:
- To investigate the impact of manganese on dopamine and homovanillic acid (HVA) levels in cirrhotic rats.
- To evaluate dopamine turnover in relation to manganese accumulation in liver failure.
Main Methods:
- Bile-duct ligation was performed on rats to induce cirrhosis.
- Rats received manganese chloride in drinking water (0.5 or 1 mg/ml).
- Striatal manganese, dopamine (DA), and homovanillic acid (HVA) levels were measured.
Main Results:
- Cirrhotic rats showed increased striatal manganese, dependent on intake.
- Dopamine levels decreased by 30% in cirrhotic rats.
- Manganese administration normalized or increased dopamine levels, with a positive correlation between Mn content and DA turnover (HVA:DA ratio).
Conclusions:
- Brain manganese accumulation in liver failure is linked to altered dopamine metabolism.
- These findings suggest manganese plays a key role in the motor abnormalities seen in human cirrhotic conditions.