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

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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 languageEnglish
Pages (from-to)129-139
Number of pages11
JournalAge
Volume36
Issue number1
DOIs
StatePublished - 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

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