title: Heterozygous knockout of the Bmi-1 gene causes an early onset of phenotypes associated with brain aging.
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.
authors.affiliation: Department of Human Anatomy, Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
authors.forename: Minxia
authors.initials: M
authors.lastname: Gu
authors.forename: Lihua
authors.initials: L
authors.lastname: Shen
authors.forename: Lei
authors.initials: L
authors.lastname: Bai
authors.forename: Junying
authors.initials: J
authors.lastname: Gao
authors.forename: Charles
authors.initials: C
authors.lastname: Marshall
authors.forename: Ting
authors.initials: T
authors.lastname: Wu
authors.forename: Jiong
authors.initials: J
authors.lastname: Ding
authors.forename: Dengshun
authors.initials: D
authors.lastname: Miao
authors.forename: Ming
authors.initials: M
authors.lastname: Xiao
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D005434:Flow Cytometry; D015870:Gene Expression; D005978:Glutathione / Q000378:metabolism; D006579:Heterozygote; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008062:Lipofuscin / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000502:physiology; D010641:Phenotype; D063150:Polycomb Repressive Complex 1 / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; C489421:Bmi1 protein, mouse; D008062:Lipofuscin; D011518:Proto-Oncogene Proteins; D017382:Reactive Oxygen Species; C002744:3-nitrotyrosine; D014443:Tyrosine; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D063150:Polycomb Repressive Complex 1; D005978:Glutathione