Memory restorative role of statins in experimental dementia: an evidence of their cholesterol dependent and independent actions.

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.

Potential of ezetimibe in memory deficits associated with dementia of Alzheimer's type in mice.

BACKGROUND: High cholesterol levels have been positively correlated with a higher incidence of memory impairment and dementia. AIM: The study was undertaken to investigate the potential of the lipid-lowering drug, ezetimibe, in memory deficits associated with dementia of Alzheimer's (AD) type in mice. METHODS: 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. The memory of the animals was assessed by employing a Morris water maze. Brain thio barbituric acid-reactive species and reduced glutathione levels were measured to assess the total oxidative stress. Brain acetyl cholinesterase (AChE) activity and total serum cholesterol levels were also measured. RESULTS: STZ/HFD produced a significant impairment of memory along with an increase in brain AChE activity and oxidative stress. HFD mice also showed an increase in cholesterol levels. Ezetimibe (10 mg/kg, orally for 15 days) significantly attenuated STZ/HFD-induced memory deficits and biochemical changes. It also prevented HFD-induced rise in the cholesterol level. CONCLUSIONS: The memory-restorative effect of ezetimibe can be attributed to its cholesterol-dependent as well as cholesterol-independent effects. The study highlights the potential of ezetimibe in memory dysfunctions associated with dementia of AD.