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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Transport System X-AG / metabolism
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Animals
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Brain / metabolism*
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Brain / pathology*
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Brain / ultrastructure
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CA1 Region, Hippocampal / enzymology
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CA1 Region, Hippocampal / pathology
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Excitatory Amino Acid Transporter 1 / metabolism
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Gliosis / metabolism
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Gliosis / pathology
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Glutamate-Ammonia Ligase / metabolism
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Mice
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Mice, Inbred C57BL
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Myelin Sheath / metabolism
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Myelin Sheath / pathology
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Neostriatum / metabolism
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Neostriatum / pathology
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Nerve Degeneration / metabolism*
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Nerve Degeneration / pathology*
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Neurons / metabolism
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Neurons / pathology
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Nuclear Proteins / deficiency*
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Nuclear Proteins / metabolism
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Oxidative Stress
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Polycomb Repressive Complex 1
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Proto-Oncogene Proteins / deficiency*
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Proto-Oncogene Proteins / metabolism
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Repressor Proteins / deficiency*
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Repressor Proteins / metabolism
Substances
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Amino Acid Transport System X-AG
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Bmi1 protein, mouse
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Excitatory Amino Acid Transporter 1
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Nuclear Proteins
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Proto-Oncogene Proteins
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Repressor Proteins
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Slc1a3 protein, mouse
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Polycomb Repressive Complex 1
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Glutamate-Ammonia Ligase