| RESEARCH ARTICLE
|Year : 2009 | Volume
| Issue : 6 | Page : 262-267
Potential of ezetimibe in memory deficits associated with dementia of Alzheimer's type in mice
Yogita Dalla1, Nirmal Singh1, Amteshwar Singh Jaggi1, Dhandeep Singh1, Pooja Ghulati2
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
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.
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab - 147 002
Source of Support: None, Conflict of Interest: None
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