Montelukast treatment protects nigral dopaminergic neurons against microglial activation in the 6-hydroxydopamine mouse model of Parkinson's disease.
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-α (TNFα) and interleukin-1β (IL-1β) 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.
aSchool of Life Sciences bBK21 Plus KNU Creative BioResearch Group cInstitute of Life Science and Biotechnology dDepartment of Biochemistry and Cell Biology, School of Medicine, Cell and Matrix Research Institute, BK21 Plus KNU Biomedical Convergence Program eBrain Science and Engineering Institute, Kyungpook National University fDepartment of Brain-Cognitive Science, Daegu-Gyeongbuk Institute of Science and Technology, Daegu gDepartment of Pharmacology hChronic Inflammatory Disease Research Center iBK21 Plus Program, Department of Biomedical Sciences, Ajou University School of Medicine, Suwon, Gyeonggi-do, Korea.
Hannah
H
Jang
Sehwan
S
Kim
Jae Man
JM
Lee
Yong-Seok
YS
Oh
Sang Myun
SM
Park
Sang Ryong
SR
Kim
D000085:Acetates / Q000494:pharmacology*; D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003521:Cyclopropanes; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D011804:Quinolines / Q000494:pharmacology*; D045442:Rotarod Performance Test; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology*; D013440:Sulfides; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000085:Acetates; D018663:Adrenergic Agents; C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D003521:Cyclopropanes; D016207:Cytokines; D008840:Microfilament Proteins; D018696:Neuroprotective Agents; D011804:Quinolines; D013440:Sulfides; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; C093875:montelukast