Levodopa exerts neuroprotective effects by suppressing microglial proinflammatory activation in a rat hemi-Parkinson’s disease model

Levodopa is a central medicine used for the treatment of Parkinson's disease (PD) as a dopamine (DA) precursor that increases DA levels in the striatum. Microglia, resident macrophages in the brain, become activated in response to the progressive degeneration of nigral dopaminergic neurons in PD pathology, while releasing proinflammatory mediators that are harmful to dopaminergic neurons. DA has been shown to prevent proinflammatory activation of microglia. This study showed that DA decreases lipopolysaccharide-induced proinflammatory reactions and increases tissue repairing factors of microglia in cultured rat microglia. Levodopa was administered to 6-hydroxydopmaine (6-OHDA)-induced PD model rats for 7 days, and motor deficits were evaluated after a two-week withdrawal period. The levodopa-treated PD model rats showed a better motor function than the vehicle-treated rats. The administration of levodopa for 7 days led to an increase in DA levels and a suppression of microglial activation in the striatum, which was maintained, even at two weeks after withdrawal. These results suggest that levodopa may act in the PD brain, not only as a DA precursor, but also as an immunosuppressant to reduce neuroinflammation accompanied by PD pathology.