Title | Heterozygous knockout of the Bmi-1 gene causes an early onset of phenotypes associated with brain aging. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Gu M, Shen L, Bai L, Gao J, Marshall C, Wu T, Ding J, Miao D, Xiao M |
Journal | Age (Dordr) |
Volume | 36 |
Issue | 1 |
Pagination | 129-39 |
Date Published | 2014 Feb |
ISSN | 1574-4647 |
Keywords | Aging, Animals, Antioxidants, Apoptosis, Biomarkers, Blotting, Western, Brain, Flow Cytometry, Gene Expression, Glutathione, Heterozygote, Immunohistochemistry, In Situ Nick-End Labeling, Lipofuscin, Male, Malondialdehyde, Maze Learning, Memory Disorders, Mice, Mice, Inbred C57BL, Oxidative Stress, Phenotype, Polycomb Repressive Complex 1, Proto-Oncogene Proteins, Reactive Oxygen Species, Superoxide Dismutase, Tyrosine |
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. |
DOI | 10.1007/s11357-013-9552-9 |
Alternate Journal | Age (Dordr) |
PubMed ID | 23771506 |
PubMed Central ID | PMC3889899 |