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Published on: March 23, 2011
Matrix metalloproteinase-12 contributes to neuroinflammation in the aged brain
Yang Liu1, Min Zhang, Wenlin Hao
1Department of Neurology, University of the Saarland, Homburg/Saar, Germany. a.liu@mx.uni-saarland.de
Abstract:
During aging the brain displays an increased proinflammatory status, which is associated with the pathogenesis of aging-related diseases such as Alzheimer's and Parkinson diseases. Matrix metalloproteinases (MMPs) facilitate the migration of inflammatory cells in tissues and modulate their inflammatory activity. In this study, we screened expression of MMPs in 3-, 10-, and 18-month-old mice and observed that cerebral MMP-12 expression was strongly upregulated during aging. We compared the neuroinflammation of 3-, 10-, and 18-month-old MMP-12-deficient versus wild type mice by counting microglia and measuring inflammatory gene transcripts in the brain and observed that MMP-12 deficiency reduced neuroinflammation during aging. In order to identify potential mechanisms, we analyzed the inflammatory activity of microglia directly isolated from adult mouse brains or cultured from newborn mice. We observed that MMP-12 deficiency increased the inflammatory activity of adult brain-derived microglia, but did not affect cultured microglia. We found greater numbers of CD11b/CD45(high) cells in the parenchyma of MMP-12 wild type than in the parenchyma of MMP-12-deficient mouse brains. Thus, our study suggested that the upregulated cerebral MMP-12 during aging enhances aging-associated neuroinflammation by facilitating recruitment of bone marrow-derived microglia into the brain.
Insights
Aging brains show increased inflammation, linked to diseases like Alzheimer's. This study found that reducing Matrix metalloproteinase-12 (MMP-12) lessens this age-related neuroinflammation by controlling inflammatory cell entry.
Area of Science:
- Neuroscience
- Immunology
- Aging Research
Background:
- The aging brain exhibits heightened inflammation, a factor in neurodegenerative diseases like Alzheimer's and Parkinson's.
- Matrix metalloproteinases (MMPs) are enzymes that influence inflammatory cell movement and activity within tissues.
Purpose of the Study:
- To investigate the role of Matrix metalloproteinase-12 (MMP-12) in age-related neuroinflammation.
- To determine if MMP-12 deficiency impacts the inflammatory status of the aging brain.
Main Methods:
- Screening of MMP expression in mice of different ages (3, 10, and 18 months).
- Comparison of neuroinflammation in MMP-12 deficient versus wild-type mice.
- Analysis of microglia and inflammatory gene transcripts in the brain.
- Assessment of microglia inflammatory activity in vitro and in vivo.
Main Results:
- Cerebral MMP-12 expression significantly increases with age in mice.
- Mice lacking MMP-12 showed reduced neuroinflammation during aging.
- MMP-12 deficiency enhanced the inflammatory activity of adult microglia but not newborn microglia.
- Increased recruitment of bone marrow-derived microglia (CD11b/CD45(high) cells) was observed in wild-type brains.
Conclusions:
- Upregulated MMP-12 in the aging brain exacerbates neuroinflammation.
- MMP-12 facilitates the recruitment of bone marrow-derived microglia into the brain, contributing to age-associated neuroinflammation.
