Simvastatin Improves Spatial Reference Memory in APP2576 Transgenic Mice

Abstract

Evidence has been presented to suggest that there is a strong relationship between the deterioration of brain cholesterol homeostasis and memory deficits. The objective of the present study is to elucidate the effects of statin on spatial reference memory in mice carrying the gene for amyloid protein. Transgenic mice APP 2576 homozygous (carrying the gene for beta amyloid protein) and wild type (control) were used in these experiments. Animals were acclimatized for one week under constant temperature and light before experimentation. Food and water were provided ad libitum. Animals (n=24) were divided into 4 groups: wild type receiving statin (10mg/kg i.p. for 7 days), wild type receiving saline, homozygous type receiving statin (10mg/kg i.p. for 7 days) and homozygous receiving saline. Spatial reference memory was assessed using the Morris Water Maze. Training for spatial reference memory began on day one of treatment, and continued for 5 consecutive days. Statin treated animals were evaluated for the maze performance on day 7. Each day of testing consisted of 2 swimming trials in the water maze. Results obtained indicate that APP 2576 homozygous mice receiving saline were unable to find the platform during the maximum allowable time (latency period of 80 seconds). However, the latency period to find the platform was significantly reduced (P<0.001) in the statin treated groups as compared to those receiving saline. The decrease in latency period following statin administration was more pronounced in the APP 2576 homozygous mice as compared to the wild type (64.3% and 45.5% decline respectively). These findings clearly indicate that simvastatin significantly improves spatial reference memory in mice carrying the gene for amyloid protein. (Supported by NIH grant RR03020)