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Memantine reduces striatal cell death with decreasing calpain level in 3-nitropropionic model of Huntington's disease

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Authors
Lee, Soon-Tae; Chu, Kon; Park, Jung-Eun; Kang, Lami; Ko, Song-Yi; Jung, Keun-Hwa; Kim, Manho
Issue Date
2006-09-09
Publisher
Elsevier
Citation
Brain Res. 2006 Nov 6;1118(1):199-207. Epub 2006 Sep 7.
Keywords
AnimalsApoptosis Regulatory Proteins/drug effects/metabolismCalpain/*drug effects/metabolismCell Death/drug effects/physiologyCorpus Striatum/*drug effects/pathology/physiopathologyDisease Models, AnimalDown-Regulation/drug effects/physiologyExcitatory Amino Acid Antagonists/pharmacology/therapeutic useHuntington Disease/*drug therapy/metabolism/physiopathologyMaleMemantine/*pharmacology/therapeutic useNerve Degeneration/*drug therapy/physiopathology/prevention & controlNerve Tissue Proteins/drug effects/metabolismNeurons/*drug effects/metabolism/pathologyNeuroprotective Agents/pharmacologyNeurotoxinsNitro CompoundsNuclear Proteins/drug effects/metabolismPeptide Fragments/drug effects/metabolismPropionic AcidsRatsRats, Sprague-Dawley
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.
ISSN
0006-8993 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16959224

http://hdl.handle.net/10371/15282
DOI
https://doi.org/10.1016/j.brainres.2006.08.035
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Neurology (신경과학교실)Journal Papers (저널논문_신경과학교실)
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