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Region‐ S pecific A lterations of M atrix M etalloproteinase A ctivity in M ultiple S ystem A trophy
Author(s) -
Bassil Fares,
Monvoisin Arnaud,
Canron MarieHelene,
Vital Anne,
Meissner Wassilios G.,
Tison François,
Fernagut PierreOlivier
Publication year - 2015
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.26329
Subject(s) - neuroinflammation , matrix metalloproteinase , myelin , pathology , biology , chemistry , microbiology and biotechnology , endocrinology , immunology , inflammation , medicine , central nervous system , biochemistry
Background MSA is a sporadic progressive neurodegenerative disorder characterized by a variable combination of parkinsonism, cerebellar ataxia, and autonomic dysfunction. The pathological hallmark of MSA is the accumulation of alpha‐synuclein aggregates in the cytoplasm of oligodendrocytes along with neuronal loss and neuroinflammation, as well as blood–brain barrier dysfunction and myelin deterioration. Matrix metalloproteinases are zinc‐dependent endopeptidases involved in the remodeling of the extracellular matrix, demyelination, and blood–brain barrier permeability. Several lines of evidence indicate a role for these enzymes in various pathological processes, including stroke, multiple sclerosis, Parkinson's, and Alzheimer's disease. Methods This study aimed to assess potential alterations of matrix metalloproteinase‐1, ‐2, ‐3, and ‐9 expression or activity in MSA postmortem brain tissue. Results Gelatin zymography revealed increased matrix metalloproteinase‐2 activity in the putamen, but not in the frontal cortex, of MSA patients relative to controls. Immunohistochemistry revealed increased number of glial cells positive for matrix metalloproteinase‐1, ‐2, and ‐3 in the putamen and frontal cortex of MSA patients. Double immunofluorescence revealed that matrix metalloproteinase‐2 and ‐3 were expressed in astrocytes and microglia. Only matrix metalloproteinase‐2 colocalized with alpha‐synuclein in oligodendroglial cytoplasmic inclusions. Conclusion These results demonstrate widespread alterations of matrix metalloproteinase expression in MSA and a pattern of increased matrix metalloproteinase‐2 expression and activity affecting preferentially a brain region severely affected (putamen) over a relatively spared region (frontal cortex). Elevated matrix metalloproteinase expression may thus contribute to the disease process in MSA by promoting blood–brain barrier dysfunction and/or myelin degradation. © 2015 International Parkinson and Movement Disorder Society