Abstract
Huntington's disease has an increase in the activated calpain, which is enhanced by the NMDA receptor activation. We investigated the neuroprotective effect of memantine in 3-nitropropionic acid (3NP)-induced striatal degeneration model. Either memantine (20 mg/kg/day) or PBS was intraperitoneally administered for five days with 3NP continuous infusion. In the memantine-treated group, the striatal lesion volume, the number of TUNEL+ cells, and Fluoro-Jade C+ degenerating neurons were all decreased. Memantine increased Bcl-xl and decreased Bax level. Memantine also exerted an inhibitory effect on the micro-calpain level and decreased the huntingtin proteolytic fragments. Those rats treated with memantine showed less degree of weight loss at 5 days. Subsequently, memantine was found to have neuroprotective effects and save striatal cells with decreasing calpain levels in the 3NP model of Huntington's disease.
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 Regulatory Proteins / drug effects
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Apoptosis Regulatory Proteins / metabolism
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Calpain / drug effects*
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Calpain / metabolism
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Cell Death / drug effects
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Cell Death / physiology
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Corpus Striatum / drug effects*
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Corpus Striatum / pathology
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Corpus Striatum / physiopathology
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Disease Models, Animal
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Down-Regulation / drug effects
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Down-Regulation / physiology
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Excitatory Amino Acid Antagonists / pharmacology
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Excitatory Amino Acid Antagonists / therapeutic use
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Huntingtin Protein
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Huntington Disease / drug therapy*
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Huntington Disease / metabolism
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Huntington Disease / physiopathology
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Male
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Memantine / pharmacology*
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Memantine / therapeutic use
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Nerve Degeneration / drug therapy*
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Nerve Degeneration / physiopathology
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Nerve Degeneration / prevention & control
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Nerve Tissue Proteins / drug effects
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Nerve Tissue Proteins / metabolism
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Neurons / drug effects*
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Neurons / metabolism
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Neurons / pathology
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Neuroprotective Agents / pharmacology
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Neurotoxins
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Nitro Compounds
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Nuclear Proteins / drug effects
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Nuclear Proteins / metabolism
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Peptide Fragments / drug effects
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Peptide Fragments / metabolism
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Propionates
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Rats
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Rats, Sprague-Dawley
Substances
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Apoptosis Regulatory Proteins
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Excitatory Amino Acid Antagonists
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Htt protein, mouse
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Huntingtin Protein
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Nerve Tissue Proteins
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Neuroprotective Agents
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Neurotoxins
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Nitro Compounds
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Nuclear Proteins
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Peptide Fragments
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Propionates
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Calpain
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3-nitropropionic acid
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Memantine