title: Bmi-1 absence causes premature brain degeneration.
abstract: Bmi-1, a polycomb transcriptional repressor, is implicated in cell cycle regulation and cell senescence. Its absence results in generalized astrogliosis and epilepsy during the postnatal development, but the underlying mechanisms are poorly understood. Here, we demonstrate the occurrence of oxidative stress in the brain of four-week-old Bmi-1 null mice. The mice showed various hallmarks of neurodegeneration including synaptic loss, axonal demyelination, reactive gliosis and brain mitochondrial damage. Moreover, astroglial glutamate transporters and glutamine synthetase decreased in the Bmi-1 null hippocampus, which might contribute to the sporadic epileptic-like seizures in these mice. These results indicate that Bmi-1 is required for maintaining endogenous antioxidant defenses in the brain, and its absence subsequently causes premature brain degeneration.
authors.affiliation: Jiangsu Province Key Laboratory of Neurodegeneration, Department of Anatomy, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Guangliang
authors.initials: G
authors.lastname: Cao
authors.forename: Minxia
authors.initials: M
authors.lastname: Gu
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.forename: Junying
authors.initials: J
authors.lastname: Gao
authors.forename: Ying
authors.initials: Y
authors.lastname: Yin
authors.forename: Charles
authors.initials: C
authors.lastname: Marshall
authors.forename: Ming
authors.initials: M
authors.lastname: Xiao
authors.forename: Jiong
authors.initials: J
authors.lastname: Ding
authors.forename: Dengshun
authors.initials: D
authors.lastname: Miao
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D056547:CA1 Region, Hippocampal / Q000201:enzymology / Q000473:pathology; D027341:Excitatory Amino Acid Transporter 1 / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism / Q000473:pathology; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D017072:Neostriatum / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000378:metabolism* / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000172:deficiency* / Q000378:metabolism; D018384:Oxidative Stress; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000172:deficiency* / Q000378:metabolism; D012097:Repressor Proteins / Q000172:deficiency* / Q000378:metabolism
chemical_list: D027322:Amino Acid Transport System X-AG; C489421:Bmi1 protein, mouse; D027341:Excitatory Amino Acid Transporter 1; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C493393:Slc1a3 protein, mouse; D063150:Polycomb Repressive Complex 1; D005974:Glutamate-Ammonia Ligase