title: Injury-stimulated Sonic hedgehog expression in microglia contributes to neuroinflammatory response in the MPTP model of Parkinson's disease.
abstract: Parkinson's disease (PD) is a progressive neurodegenerative disorder in which dopamine (DA) neurons in the substantia nigra pars compacta (SNpc) region are selectively destroyed. Sonic hedgehog (Shh) has been well known to play a key role in a variety of processes such as embryogenesis, cell proliferation and protection, and tissue repair during inflammation. However, the evidences for the innate role of Shh in adult brain injury are presently lacking and studies have been needed to unveil the importance of Shh in the process of neurodegeneration. Here, we investigated the role of Shh in the pathologic progress of Parkinson's disease in MPTP-induced animal model system. Interestingly, we observed that Shh expression was gradually increased in MPTP affected SNpc region. Activated microglia exclusively expressed SHH in vivo and we could recapitulate Shh induction in activated cultured primary microglia cells. Using the SHH responsive Cre-loxP binary genetic reporter transgenic mouse system, we also found that most of the cell types except for oligodendrocyte in the SNpc region reacted to the SHH by MPTP injection. Taken together, activated microglia induced Shh expression and most neural cells except oligodendrocyte responded to microglia-derived SHH in MPTP-treated SN. These results suggest that SHH in activated microglia by MPTP-injection might be involved in the innate processes of recovery from neurotoxin induced injury in the PD animal model system.
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Goyang 410-820, South Korea; Department of Biochemistry & Molecular Biology, School of Medicine Kyung Hee University, Seoul 130-701, South Korea.
authors.forename: Jeong Hwi
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Biochemistry & Molecular Biology, School of Medicine Kyung Hee University, Seoul 130-701, South Korea.
authors.forename: Young Cheul
authors.initials: YC
authors.lastname: Chung
authors.affiliation: Department of Biochemistry & Molecular Biology, School of Medicine Kyung Hee University, Seoul 130-701, South Korea.
authors.forename: Eugene
authors.initials: E
authors.lastname: Bok
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Goyang 410-820, South Korea.
authors.forename: Hankyu
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Biochemistry & Molecular Biology, School of Medicine Kyung Hee University, Seoul 130-701, South Korea.
authors.forename: Sue Hee
authors.initials: SH
authors.lastname: Huh
authors.affiliation: Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 135-710, South Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Biochemistry & Molecular Biology, School of Medicine Kyung Hee University, Seoul 130-701, South Korea. Electronic address: bkjin@khu.ac.kr.
authors.forename: Byung Kwan
authors.initials: BK
authors.lastname: Jin
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Goyang 410-820, South Korea. Electronic address: kohw@dongguk.edu.
authors.forename: Hyuk Wan
authors.initials: HW
authors.lastname: Ko
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D053823:Hedgehog Proteins / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008810:Mice, Inbred C57BL; D017628:Microglia; D010302:Parkinson Disease, Secondary / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D013378:Substantia Nigra / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation
chemical_list: D053823:Hedgehog Proteins; D008070:Lipopolysaccharides; C465570:Shh protein, mouse; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
keywords: MPTP; Microglia; Parkinson's disease; Sonic hedgehog