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Heterozygous knockout of the Bmi-1 gene causes an early onset of phenotypes associated with brain aging
- Source :
- Age (Dordrecht, Netherlands). 36(1)
- Publication Year :
- 2012
-
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.
- Subjects :
- Male
medicine.medical_specialty
Aging
Heterozygote
Blotting, Western
Morris water navigation task
Hippocampus
Gene Expression
Apoptosis
medicine.disease_cause
Antioxidants
Article
Lipofuscin
Superoxide dismutase
chemistry.chemical_compound
Mice
Downregulation and upregulation
Internal medicine
Malondialdehyde
Proto-Oncogene Proteins
medicine
In Situ Nick-End Labeling
Aging brain
Animals
Maze Learning
Gene knockout
Polycomb Repressive Complex 1
Memory Disorders
biology
Superoxide Dismutase
Nitrotyrosine
nutritional and metabolic diseases
Brain
General Medicine
Flow Cytometry
Molecular biology
Glutathione
Immunohistochemistry
Mice, Inbred C57BL
Oxidative Stress
Endocrinology
Phenotype
chemistry
biology.protein
Tyrosine
Geriatrics and Gerontology
Reactive Oxygen Species
Oxidative stress
Biomarkers
Subjects
Details
- ISSN :
- 15744647
- Volume :
- 36
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Age (Dordrecht, Netherlands)
- Accession number :
- edsair.doi.dedup.....bc3c9e7a6330a834fd7571a7f5a41b43