Treatment with Simvastatin, one of the statin drugs widely used for lowering cholesterol in humans, significantly improved spatial memory - how to navigate a water maze - in mice genetically bred to have an Alzheimer's like disease. Although statin improved memory in both males and females, the results were more pronounced in males.
Dr. H. A. Morcos, chair of Pharmacology at the American University of Antigua, and colleagues at Florida A & M University presented the study April 30 at Experimental Biology 2007 in Washington, DC. His presentation is part of the scientific program of the American Society for Pharmacology and Experimental Therapeutics.
The study confirmed the Morcos laboratory's earlier findings of improved memory in this mouse model of Alzheimer's and discovered new information about the neurochemical basis of the beneficial effects. Various studies have found evidence of a strong relationship between memory deficits and high levels of cholesterol in the brain, suggesting that statin's effects on memory might be due to a reduction in cholesterol biosynthesis.
In this study, Dr. Morcos found that nNOS (neuronal nitric oxide synthase) levels were significantly higher in the hippocampus and cortex of statin treated groups as compared to similar mice that did not receive statin. Furthermore, the levels of nNOS proteins were statistically higher in the hippocampus of the statin treated animals than in the cortex. nNOS is responsible for the release of nitric oxide, a substance that causes dilation of the blood vessels in the brain, which eventually will increase blood flow and improve circulation to the memory region of the brain. These findings suggest that increases in brain nNos levels may play an important role in statin-induced improvement of spatial reference memory.
The transgenic mice used in the study are homozygous for the gene for beta amyloid protein, making it inevitable that they develop an Alzheimer's like disease as they age. In fact, they lose their memory by nine months of age. These animals, together with regular mice without the beta amyloid genes, were acclimated for one week, with as much food and water as they wished, then divided into four groups. Half the "Alzheimer's mice" and half the normal mice received 10 mg/kg Simvastatin for seven days, while half of each group only received saline. Each day the mice had two swimming trials in the water maze, giving them a chance to learn how to reach a platform. Food was always available and safety makes taken during the entire trial.
On the seventh day the animals were tested for spatial memory, in other words low long it took them to find the platform. The Alzheimer's mice that received statin were able to find the platform while none of the transgenic mice receiving only saline were able to do so. Normal mice on statin also showed improvement in the time they usually take to reach the platform compared to normal mice on saline. After the maze test, brain tissue then was studied to determine levels of nNOS.