Memantine reduces striatal cell death with decreasing calpain level in 3-nitropropionic model of Huntington's disease.
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.
Lee
Soon-Tae
ST
Department of Neurology, Clinical Research Institute, Seoul National University Hospital, Chongro-Gu, Seoul, South Korea.
Chu
Kon
K
Park
Jung-Eun
JE
Kang
Lami
L
Ko
Song-Yi
SY
Jung
Keun-Hwa
KH
Kim
Manho
M
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000378:metabolism; D002154:Calpain / Q000187:drug effects* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008559:Memantine / Q000494:pharmacology* / Q000627:therapeutic use; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins; D009574:Nitro Compounds; D009687:Nuclear Proteins / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism; D011422:Propionates; D051381:Rats; D017207:Rats, Sprague-Dawley
D051017:Apoptosis Regulatory Proteins; D018691:Excitatory Amino Acid Antagonists; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D009574:Nitro Compounds; D009687:Nuclear Proteins; D010446:Peptide Fragments; D011422:Propionates; D002154:Calpain; C015392:3-nitropropionic acid; D008559:Memantine