Dalla_2010_Pharmacol.Rep_62_784

The study was aimed at investigating the effects of pitavastatin, simvastatin (lipophilic statins) and fluvastatin (hydrophilic statin) on memory deficits associated with Alzheimer's type dementia in mice. Dementia was induced with chronic administration of a high fat diet (HFD) or intracebroventricular streptozotocin (icv STZ, two doses of 3 mg/kg) in separate groups of animals. Memory of the animals was assessed by the Morris water maze (MWM) test. Brain thiobarbituric acid reactive species (TBARS) and reduced glutathione (GSH) levels were measured to assess total oxidative stress. Brain acetylcholinesterase (AChE) activity and total serum cholesterol levels were also measured. Icv STZ or HFD produced a significant impairment of learning and memory. Higher levels of brain AChE activity and TBARS and lower levels of GSH were observed in icv STZ- as well as HFD-treated animals. HFD-treated mice also showed a significant increase in total serum cholesterol levels. Pitavastatin and simvastatin each significantly attenuated STZ-induced memory deficits and biochemical changes; however, fluvastatin produced no significant effect on icv STZ-induced dementia or biochemical levels. Administration of any one of the three statins not only lowered HFD-induced rise in total serum cholesterol level but also attenuated HFD-induced memory deficits. Further pitavastatin and simvastatin administration also reversed HFD-induced changes in biochemicals level, while fluvastatin failed to produce any significant effect. This study demonstrates the potential of statins in memory dysfunctions associated with experimental dementia and provides evidence of their cholesterol-dependent and -independent actions.