Author(s)

Steven Lowrance, Jessica Matchynski, Julien Rossignol, Nicholas Dekorver, Michael Sandstrom, Gary Dunbar

Field Neurosciences Institute Laboratory for Restorative Neurology.
Program in Neuroscience.

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.

Alzheimer’s Disease; Memory Deficits; Substituted Pyrimidines; Mu-p-75 Saporin; Morris Water Maze

S. Lowrance, J. Matchynski, J. Rossignol, N. Dekorver, M. Sandstrom and G. Dunbar, "CXB-909 Attenuates Cognitive Deficits in the Mu-P-75 Saporin Mouse Model of Alzheimer’s Disease," Neuroscience and Medicine, Vol. 3 No. 1, 2012, pp. 65-68. doi: 10.4236/nm.2012.31010.