Abnormal Motor Function and the Expression of Striatal Dopamine D2 Receptors in Manganese-Treated Mice(Molecular and Cell Biology)

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Manganese (Mn) plays an important role in the etiology of several neurobehavioral disorders, but there is a lack of data regarding its specific effects on neurotransduction, especially dopaminergic neurotransduction. We investigated the relationship between motor deficits and alterations in the expression of tyrosine hydroxylase (TH) and dopamine D2-like receptors (DR), including the three dopaminergic subtypes, D2, D3, and D4, in low- and high-dose Mn-treated mice. After administration of Mn (intraperitoneal injections of 20 or 40mg/kg MnCl_2・4H_2O once per day for 5d), motor activity and expression of TH and DR were examined in the striatum of the mouse brain. Mn treatment resulted in significant decrease in coordination and/or impaired motor learning after 5d of treatment and this effect remained until 10d after the end of Mn treatment. The expression of dopamine D2-like receptor D2 (DRD2), but not TH, DRD3, or DRD4, in the striatum was dose-dependent, and statistically significant increases were seen at the mRNA and protein levels. These findings indicate that Mn-induced motor deficits may be modulated in part by the expression of DRD2 in the striatum. In addition, our results suggest that the disturbance of dopaminergic neurotransmission mediated by DRD2 may be involved in the pathogenesis of Mn neurotoxicity.
公益社団法人日本薬学会の論文
2008-10-01