, Volume 36, Issue 1, pp 129–139

Heterozygous knockout of the Bmi-1 gene causes an early onset of phenotypes associated with brain aging

  • Minxia Gu
  • Lihua Shen
  • Lei Bai
  • Junying Gao
  • Charles Marshall
  • Ting Wu
  • Jiong Ding
  • Dengshun Miao
  • Ming Xiao


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.


Bmi-1 Brain aging Reactive oxygen species Reactive gliosis 

Supplementary material

11357_2013_9552_MOESM1_ESM.pdf (170 kb)
ESM 1PDF 170 kb


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Copyright information

© American Aging Association 2013

Authors and Affiliations

  • Minxia Gu
    • 1
  • Lihua Shen
    • 1
  • Lei Bai
    • 1
  • Junying Gao
    • 1
  • Charles Marshall
    • 3
  • Ting Wu
    • 2
  • Jiong Ding
    • 1
  • Dengshun Miao
    • 1
  • Ming Xiao
    • 1
  1. 1.Department of Human AnatomyNanjing Medical UniversityNanjingChina
  2. 2.Department of Neurologythe First Affiliated Hospital of Nanjing Medical University NanjingJiangsuChina
  3. 3.Department of Rehabilitation SciencesUniversity of Kentucky Center for Excellence in Rural HealthHazardUSA

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