Abstract
This study was undertaken to investigate the potential role of cell cycle re-entry in an experimental model of Huntington's disease and in human brain samples. We found that after treatment of rats with the mitochondrial neurotoxin 3-nitropropionic acid, the expression of cell cycle markers of G1 phase measured by immunohistochemistry was induced in the striatal brain region. Furthermore, we detected an increase in the nuclear and also cytoplasmatic E2F-1 expression, suggesting that this protein could activate the apoptotic cascade in rat brain. Western blot analysis of post-mortem brain samples from patients also showed an increase in the expression of E2F-1 and cyclin D1 in comparison with control samples. These results indicate that cell cycle re-entry is activated in Huntington's disease and may contribute to the neurodegenerative process.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects
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Apoptosis / physiology
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Convulsants / toxicity
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Corpus Striatum / metabolism*
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Corpus Striatum / physiopathology
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Cyclin D1 / genetics
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Cyclin D1 / metabolism
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Disease Models, Animal
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Dyskinesia, Drug-Induced / genetics
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Dyskinesia, Drug-Induced / metabolism
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Dyskinesia, Drug-Induced / physiopathology
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E2F1 Transcription Factor / genetics
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E2F1 Transcription Factor / metabolism
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Female
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G1 Phase / drug effects
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G1 Phase / genetics
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / genetics
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Genes, cdc / physiology*
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Humans
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Huntington Disease / genetics
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Huntington Disease / metabolism*
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Huntington Disease / physiopathology
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Male
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Nerve Degeneration / genetics
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Nerve Degeneration / metabolism*
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Nerve Degeneration / physiopathology
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Neurons / metabolism*
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Neurotoxins / toxicity
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Nitro Compounds / toxicity
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Propionates / toxicity
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Rats
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Rats, Sprague-Dawley
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Up-Regulation / drug effects
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Up-Regulation / genetics
Substances
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Cell Cycle Proteins
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Convulsants
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E2F1 Transcription Factor
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Neurotoxins
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Nitro Compounds
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Propionates
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Cyclin D1
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3-nitropropionic acid