title: Capsaicin prevents degeneration of dopamine neurons by inhibiting glial activation and oxidative stress in the MPTP model of Parkinson's disease.
abstract: The effects of capsaicin (CAP), a transient receptor potential vanilloid subtype 1 (TRPV1) agonist, were determined on nigrostriatal dopamine (DA) neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). The results showed that TRPV1 activation by CAP rescued nigrostriatal DA neurons, enhanced striatal DA functions and improved behavioral recovery in MPTP-treated mice. CAP neuroprotection was associated with reduced expression of proinflammatory cytokines (tumor necrosis factor-α and interleukin-1β) and reactive oxygen species/reactive nitrogen species from activated microglia-derived NADPH oxidase, inducible nitric oxide synthase or reactive astrocyte-derived myeloidperoxidase. These beneficial effects of CAP were reversed by treatment with the TRPV1 antagonists capsazepine and iodo-resiniferatoxin, indicating TRPV1 involvement. This study demonstrates that TRPV1 activation by CAP protects nigrostriatal DA neurons via inhibition of glial activation-mediated oxidative stress and neuroinflammation in the MPTP mouse model of PD. These results suggest that CAP and its analogs may be beneficial therapeutic agents for the treatment of PD and other neurodegenerative disorders that are associated with neuroinflammation and glial activation-derived oxidative damage.
authors.affiliation: College of Pharmacy, Dongguk University, Goyang, Republic of Korea.
authors.forename: Young C
authors.initials: YC
authors.lastname: Chung
authors.affiliation: Department of Neuroscience, Graduate School, Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Jeong Y
authors.initials: JY
authors.lastname: Baek
authors.affiliation: School of Life Sciences, BK21 plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea.|Brain Science and Engineering Institute, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Sang R
authors.identifier: 0000-0003-0299-1613
authors.initials: SR
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Dongguk University, Goyang, Republic of Korea.
authors.forename: Hyuk W
authors.initials: HW
authors.lastname: Ko
authors.affiliation: Brain Science and Engineering Institute, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Eugene
authors.initials: E
authors.lastname: Bok
authors.affiliation: Predictive model Research Center, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
authors.forename: Won-Ho
authors.initials: WH
authors.lastname: Shin
authors.affiliation: Department of Biochemistry and Signaling Disorder Research Center, College of Medicine, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: So-Yoon
authors.initials: SY
authors.lastname: Won
authors.affiliation: Department of Neuroscience, Graduate School, Kyung Hee University, Seoul, Republic of Korea.|Department of Biochemistry and Molecular Biology, Neurodegeneration Control Research Center, School of Medicine Kyung Hee University, Seoul, Republic of Korea.
authors.forename: Byung K
authors.initials: BK
authors.lastname: Jin
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D002211:Capsaicin / Q000494:pharmacology* / Q000627:therapeutic use; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D020267:MPTP Poisoning / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019255:NADPH Oxidases / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D052247:Nitric Oxide Synthase Type II; D019255:NADPH Oxidases; D002211:Capsaicin