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.


OBJECTIVE
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.
Dalla
Yogita
Y
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab - 147 002, India.
Singh
Nirmal
N
Jaggi
Amteshwar Singh
AS
Singh
Dhandeep
D
Ghulati
Pooja
P
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