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

Authors
Jang, H; Kim, S; Lee, JM; Oh, YS; Park, SM; Kim, SR
Citation
Neuroreport, 28(5):242-249, 2017
Journal Title
Neuroreport
ISSN
0959-49651473-558X
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.
MeSH terms
Acetates/pharmacology*Adrenergic Agents/toxicityAnimalsCalcium-Binding Proteins/metabolismCytokines/metabolismDisease Models, AnimalDopaminergic Neurons/drug effects*Dopaminergic Neurons/metabolismDose-Response Relationship, DrugMaleMiceMice, Inbred C57BLMicrofilament Proteins/metabolismMicroglia/drug effects*Neuroprotective Agents/pharmacology*Oxidopamine/toxicityParkinson Disease/drug therapyParkinson Disease/etiologyParkinson Disease/pathology*Quinolines/pharmacology*Rotarod Performance TestSubstantia Nigra/drug effectsSubstantia Nigra/pathology*Tyrosine 3-Monooxygenase/metabolism
DOI
10.1097/WNR.0000000000000740
PMID
28178069
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
박, 상면
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