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Hyperoxygenation Treatment Reduces Beta-amyloid Deposition via MeCP2-dependent Upregulation of MMP-2 and MMP-9 in the Hippocampus of Tg-APP/PS1 Mice

Title
Hyperoxygenation Treatment Reduces Beta-amyloid Deposition via MeCP2-dependent Upregulation of MMP-2 and MMP-9 in the Hippocampus of Tg-APP/PS1 Mice
Authors
Choi, JuliKwon, HyejinHan, Pyung-Lim
Ewha Authors
한평림
SCOPUS Author ID
한평림scopus
Issue Date
2021
Journal Title
EXPERIMENTAL NEUROBIOLOGY
ISSN
1226-2560JCR Link

2093-8144JCR Link
Citation
EXPERIMENTAL NEUROBIOLOGY vol. 30, no. 4, pp. 294 - 307
Keywords
HyperoxygenationBeta-amyloidMeCP2MMP-2MMP-9
Publisher
KOREAN SOC BRAIN &

NEURAL SCIENCE, KOREAN SOC NEURODEGENERATIVE DISEASE
Indexed
SCIE; SCOPUS; KCI WOS
Document Type
Article
Abstract
Recently we reported that hyperoxygenation treatment reduces amyloid-beta accumulation and rescues cognitive impairment in the Tg-APP/PS1 mouse model of Alzheimer's disease. In the present study, we continue to investigate the mechanism by which hyperoxygenation reduces amyloidbeta deposition in the brain. Hyperoxygenation treatment induces upregulation of matrix metalloproteinase-2 (MMP-2), MMP-9, and tissue plasminogen activator (tPA), the endopeptidases that can degrade amyloid-beta, in the hippocampus of Tg-APP/PS1 mice. The promoter regions of the three proteinase genes all contain potential binding sites for MeCP2 and Pea3, which are upregulated in the hippocampus after hyperoxygenation. Hyperoxygenation treatment in HT22 neuronal cells increases MeCP2 but not Pea3 expression. In HT22 cells, siRNA-mediated knockdown of Mecp2 decreases Mmp-9 expression and to a lesser extent, Mmp-2 and tPA expression. In mice, siRNA-mediated Mecp2 knockdown in the hippocampus reduces Mmp-9 expression, but not significantlyMmp-2 and tPA expression. The ChIP assay indicates that hyperoxygenation treatment in Tg-APP/PS1 mice increases MeCP2 binding to the promoter regions of Mmp-2, Mmp-9 and tPA genes in the hippocampus. Together, these results suggest that hyperoxygenation increases the expression of MMP-2, MMP-9, and tPA, of which MMP-9 is upregulated via MeCP2 in neuronal cells, and MMP-2 and tPA are upregulated through MeCP2 and other nuclear factors.
DOI
10.5607/en21014
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일반대학원 > 뇌·인지과학과 > Journal papers
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