Striatal manganese accumulation induces changes in dopamine metabolism in the cirrhotic rat

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.