Simvastatin increases nNOS protein expression in hippocampus and cortex of APP2576 transgenic mice

Abstract

Previous results obtained in our lab indicate that statin statistically improves the spatial reference memory in APP 2576 transgenic mice (carrying the gene for beta amyloid protein) and wild type (control) as tested by the Morris Water maze. The objective of the present study is to identify the neurochemical basis of the beneficial effects of statin on spatial reference memory. 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 simvastatin(10mg/kg i.p. for 7 days), wild type receiving saline, homozygous type receiving simvastatin (10mg/kg i.p. for 7 days) and homozygous receiving saline. Animals were sacrificed after spatial memory testing and their brains immediately removed and dissected. Neuronal nitric oxide synthase (nNOS) levels were determined by Western Blot analysis in both the hippocampus and cortex. Results obtained indicate that nNOS levels were significantly higher in the hippocampus and cortex of statin treated groups as compared to controls (p<0.05). The levels of nNOS were also statistically higher in the hippocampus of the statin treated group when compared to those in the cortex. These results clearly indicate that simvastatin significantly increases nNOS levels in the hippocampus and cortex of treated mice. These findings suggest that increases in brain nNOS levels may play an important role in statin-induced improvement of spatial reference memory. (Supported by NIH grant RR03020)