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 RESEARCH ARTICLE
Year : 2009  |  Volume : 41  |  Issue : 6  |  Page : 262-267

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


1 Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab - 147 002, India
2 Swami Vivekanand College of Pharmacy, SVIET, Chandigarh Highway, Rajpura, India

Correspondence Address:
Nirmal Singh
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab - 147 002
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0253-7613.59925

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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.






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