Effects of statins and cholesterol on memory functions in mice

Studies on influence of lipid lowering therapies have generated wide controversial results on the role of cholesterol on memory function. However recent studies revealed that cholesterol lowering treatment substantially reduce the risk of dementia. The objectives of this study were to analyze the effect of statins on memory function and to establish the relationship between increase/decrease in cholesterol synthesis, total cholesterol level and memory function in animals. We examined the relationship between biosynthesis of cholesterol and memory function using two statins (lipophilic simvastatin and hydrophilic pravastatin) and high cholesterol diet in mice for 15 days and 4 months. Memory performance was evaluated with two different behavioral tests and various biochemical parameters such as serum cholesterol, whole brain cholesterol, brain 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) activity and brain acetylcholine esterase (AChE) activity. We found that statin treatment for 4 months, but not for 15 days, showed significant improvement in memory function whereas high cholesterol diet showed significant impairment of memory. However long-term statin treatment showed significant decrease in serum cholesterol level as well as brain AChE level. Moreover high cholesterol diet showed significant decrease in memory function with an increase in serum cholesterol level as well as brain AChE level. There is no direct correlation between brain cholesterol level, as well as HMG-CoA activity with memory function regulation. However there is definite link between plasma cholesterol level and AChE level. A long-standing plasma cholesterol alteration may be essential to regulate memory function which in turn might be mediated through AChE modulated pathway.