Montelukast treatment protects nigral dopaminergic neurons against microglial activation in the 6-hydroxydopamine mouse model of Parkinson's disease

Abstract

Although the main cause of degeneration of the nigrostriatal dopaminergic (DA) projection in Parkinson's disease (PD) is still controversial, many reports suggest that excessive inflammatory responses mediated by activated microglia can induce neurotoxicity in the nigrostriatal DA system in vivo. Montelukast, which plays an anti-inflammatory role, is used to treat patients with asthma. In addition, recent studies have reported that its administration could reduce neuroinflammatory activities, showing beneficial effects against various neuropathological conditions. These results suggest that montelukast may be a useful drug to alleviate inflammatory responses in PD, even though there are no reports showing its beneficial effects against neurotoxicity in the nigrostriatal DA system. In the present study, our results showed that treatment with montelukast could protect DA neurons against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity and its administration significantly attenuated the production of neurotoxic cytokines such as tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta) from activated microglia in the substantia nigra (SN) and striatum following 6-OHDA treatment. Therefore, we suggest that montelukast can be used as a potential inhibitor of microglial activation to protect DA neurons in the adult brain against PD.