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.