Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab - 147 002, India.
Indian J Pharmacol. 2009 Dec;41(6):262-7. doi: 10.4103/0253-7613.59925.
High cholesterol levels have been positively correlated with a higher incidence of memory impairment and dementia.
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.
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.
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.
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.
高胆固醇水平与记忆障碍和痴呆的发生率升高呈正相关。
本研究旨在探讨降脂药依折麦布对阿尔茨海默病（AD）型痴呆相关记忆缺陷的潜在作用。
在两组动物中，通过给予高脂肪饮食（HFD）或侧脑室链脲佐菌素（ICV STZ，两次剂量为 3 mg/kg）来诱导痴呆。通过 Morris 水迷宫评估动物的记忆。测量脑硫代巴比妥酸反应性物质和还原型谷胱甘肽水平以评估总氧化应激。还测量脑乙酰胆碱酯酶（AChE）活性和总血清胆固醇水平。
STZ/HFD 导致记忆明显受损，同时脑 AChE 活性和氧化应激增加。HFD 小鼠的胆固醇水平也升高。依折麦布（10 mg/kg，口服 15 天）显著减轻了 STZ/HFD 诱导的记忆缺陷和生化变化。它还防止了 HFD 诱导的胆固醇水平升高。
依折麦布的记忆恢复作用可归因于其依赖胆固醇和非依赖胆固醇的作用。该研究强调了依折麦布在与 AD 痴呆相关的记忆功能障碍中的潜在作用。
