Abstract
Previous studies reported that the polycomb group gene Bmi-1 is downregulated in the aging brain. The aim of this study was to investigate whether decreased Bmi-1 expression accelerates brain aging by analyzing the brain phenotype of adult Bmi-1 heterozygous knockout (Bmi-1+/-) mice. An 8-month-old Bmi-1+/- brains demonstrated mild oxidative stress, revealed by significant increases in hydroxy radical and nitrotyrosine, and nonsignificant increases in reactive oxygen species and malonaldehyde compared with the wild-type littermates. Bmi-1+/- hippocampus had high apoptotic percentage and lipofuscin deposition in pyramidal neurons associated with upregulation of cyclin-dependent kinase inhibitors p19, p27, and p53 and downregulation of anti-apoptotic protein Bcl-2. Mild activation of astrocytes was also observed in Bmi-1+/- hippocampus. Furthermore, Bmi-1 +/- mice showed mild spatial memory impairment in the Morris Water Maze test. These results demonstrate that heterozygous Bmi-1 gene knockout causes an early onset of age-related brain changes, suggesting that Bmi-1 has a role in regulating brain aging.
Original language | English |
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Pages (from-to) | 129-139 |
Number of pages | 11 |
Journal | Age |
Volume | 36 |
Issue number | 1 |
DOIs | |
State | Published - Feb 2014 |
Bibliographical note
Funding Information:Acknowledgments We would like to thank Professor Anton Berns in the Netherlands Cancer Institute for providing Bmi1+/− mice. This work was supported by grants from the National Natural Science Foundation of China (nos. 30971020 and 81271210 to
Keywords
- Bmi-1
- Brain aging
- Reactive gliosis
- Reactive oxygen species
ASJC Scopus subject areas
- Aging
- Geriatrics and Gerontology