CXB-909 Attenuates Cognitive Deficits in the Mu-P-75 Saporin Mouse Model of Alzheimer’s Disease  

作　　者：Steven Lowrance Jessica Matchynski Julien Rossignol Nicholas Dekorver Michael Sandstrom Gary Dunbar 

机构地区：[1]Field Neurosciences Institute Laboratory for Restorative Neurology [2]Program in Neuroscience

出　　处：《Neuroscience & Medicine》2012年第1期65-68,共4页神经系统科学与医药（英文）

摘　　要：The purpose of this study was to determine if the substituted pyrimidine, CXB-909 (formerly known as KP544) which has been shown to amplify the effects of nerve growth factor in elevating choline-acetyltransferase activity in vitro, could attenuate memory deficits in the mu-p-75 saporin injected mouse model of Alzheimer’s disease (AD). Seventy-one, seven-week old C57/BL6 mice received daily oral intubation of 10, 15, or 20 mg/kg CXB-909, or vehicle (0.5% methylcellulose solution), which continued for 32 days. At postnatal week nine, mice received bilateral intra-cerebroventricular injections of mu-p-75 saporin, or sterile phosphate buffered saline. Seven days after surgery, mice were trained for two days, on a cued-platform version of the Morris water maze task, and then tested on a four-day hidden-platform version, followed by a one-day probe version of this task. Mice injected with mu-p-75 saporin, had increased latency to find the hidden-platform compared to sham mice. Furthermore, mice treated with CXB-909 at the 10, and 15 mg/kg doses, significantly reduced their latency to reach the hidden-platform, compared to vehicle-treated mice given mu-p-75 saporin. These results suggest that CXB-909 can attenuate memory deficits in the mu-p-75 saporin injected mouse model of AD.The purpose of this study was to determine if the substituted pyrimidine, CXB-909 (formerly known as KP544) which has been shown to amplify the effects of nerve growth factor in elevating choline-acetyltransferase activity in vitro, could attenuate memory deficits in the mu-p-75 saporin injected mouse model of Alzheimer’s disease (AD). Seventy-one, seven-week old C57/BL6 mice received daily oral intubation of 10, 15, or 20 mg/kg CXB-909, or vehicle (0.5% methylcellulose solution), which continued for 32 days. At postnatal week nine, mice received bilateral intra-cerebroventricular injections of mu-p-75 saporin, or sterile phosphate buffered saline. Seven days after surgery, mice were trained for two days, on a cued-platform version of the Morris water maze task, and then tested on a four-day hidden-platform version, followed by a one-day probe version of this task. Mice injected with mu-p-75 saporin, had increased latency to find the hidden-platform compared to sham mice. Furthermore, mice treated with CXB-909 at the 10, and 15 mg/kg doses, significantly reduced their latency to reach the hidden-platform, compared to vehicle-treated mice given mu-p-75 saporin. These results suggest that CXB-909 can attenuate memory deficits in the mu-p-75 saporin injected mouse model of AD.

关 键 词：Alzheimer’s Disease Memory Deficits Substituted PYRIMIDINES Mu-p-75 SAPORIN MORRIS Water Maze 

分 类 号：R73[医药卫生—肿瘤]