title: MMP-3 contributes to nigrostriatal dopaminergic neuronal loss, BBB damage, and neuroinflammation in an MPTP mouse model of Parkinson's disease.
abstract: The present study examined whether matrix metalloproteinase-3 (MMP-3) participates in the loss of dopaminergic (DA) neurons in the nigrostriatal pathway in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease with blood brain barrier (BBB) damage and infiltration of peripheral immune cells. Tyrosine hydroxylase (TH) immunostaining of brain sections from MPTP-treated mice showed that MPTP induced significant degeneration of nigrostriatal DA neurons. Moreover, FITC-labeled albumin detection and immunostaining revealed that MPTP caused damage to the BBB and increased the number of ED-1- and CD-3-immunopositive cells in the substantia nigra (SN). Genetic ablation of MMP-3 reduced the nigrostriatal DA neuron loss and improved motor function. This neuroprotective effect afforded by MMP-3 deletion was associated with the suppression of BBB disruption and a decrease in the number of ED-1- and CD-3-immunopositive cells in the SN. These data suggest that MMP-3 could play a crucial role in neurodegenerative diseases such as PD in which BBB damage and neuroinflammation are implicated.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Young Cheul
authors.initials: YC
authors.lastname: Chung
authors.forename: Yoon-Seong
authors.initials: YS
authors.lastname: Kim
authors.forename: Eugene
authors.initials: E
authors.lastname: Bok
authors.forename: Tae Young
authors.initials: TY
authors.lastname: Yune
authors.forename: Sungho
authors.initials: S
authors.lastname: Maeng
authors.forename: Byung Kwan
authors.initials: BK
authors.lastname: Jin
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000473:pathology*; D003720:Densitometry; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology*; D010587:Phagocytosis; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D014446:Tyrosine 3-Monooxygenase; D019278:Matrix Metalloproteinase 3; C511769:Mmp3 protein, mouse; D004298:Dopamine