摘要
背景:虽然临床维生素A缺乏症(VAD)是世界范围内发展的公共卫生问题,但受到很好的控制,边缘性维生素A缺乏症(MVAD)更是普遍存在,特别是在中国孕妇和学龄前儿童中。越来越多的证据表明,VAD参与了阿尔茨海默病(AD)的发病机制。然而,MVAD是否从早期开始,增加AD发展的风险尚未确定。 目的:本研究的目的是探讨MVAD对大鼠AD发病机制的长期影响。 方法:从母体MVAD大鼠产生MVAD模型,断奶后用MVAD饮食维持。将男性双侧注射聚集的淀粉样蛋白β(Aβ)1-42进入海马的CA3区域,并检查与AD相关的认知和神经病理学表型。 结果:我们发现MVAR喂养显着加重了Morris水迷宫测试中Aβ1-42诱导的学习和记忆缺陷。在Aβ1-42注射的大鼠中,MVAD不诱导维甲酸受体(RARs),解联蛋白和金属蛋白酶10(ADAM10)或胰岛素降解酶(IDE)的mRNA表达。此外,RARα和RARγmRNA与ADAM10 mRNA呈正相关,而RARβmRNA与IDE mRNA呈正相关。 结论:我们的研究表明,从胚胎期开始的MVAD扰乱了AD相关基因,导致发展AD的风险增加。
关键词: 阿尔茨海默病,淀粉样蛋白β,维生素A,边缘维生素A缺乏症,记忆障碍,视黄酸受体,ADAM10,IDE。
Current Alzheimer Research
Title:Marginal Vitamin A Deficiency Exacerbates Memory Deficits Following Aβ1-42 Injection in Rats
Volume: 14 Issue: 5
关键词: 阿尔茨海默病,淀粉样蛋白β,维生素A,边缘维生素A缺乏症,记忆障碍,视黄酸受体,ADAM10,IDE。
摘要: Background: Although clinical vitamin A deficiency (VAD), which is a public health problem developing throughout the world, has been well controlled, marginal vitamin A deficiency (MVAD) is far more prevalent, especially among pregnant women and preschool children in China. Increasing evidence suggests that VAD is involved in the pathogenesis of Alzheimer’s disease (AD). However, whether MVAD, beginning early in life, increases the risk of developing AD has yet to be determined.
Objective: The goal of this study was to investigate the long-term effects of MVAD on the pathogenesis of AD in rats. Method: An MVAD model was generated from maternal MVAD rats and maintained with an MVAD diet after weaning. The males were bilaterally injected with aggregated amyloid β (Aβ)1–42 into the CA3 area of the hippocampus, and the AD-associated cognitive and neuropathological phenotypes were examined. Results: We found that MVAD feeding significantly aggravated Aβ1-42-induced learning and memory deficits in the Morris water maze test. MVAD did not induce the mRNA expression of retinoic acid receptors (RARs), a disintegrin and metalloprotease 10 (ADAM10) or insulin-degrading enzyme (IDE) in Aβ1-42-injected rats. Moreover, RARα and RARγ mRNA were positively correlated with ADAM10 mRNA, whereas RARβ mRNA was positively correlated with IDE mRNA. Conclusion: Our study suggests that MVAD beginning from the embryonic period perturbs the ADassociated genes, resulting in an enhanced risk of developing AD.Export Options
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Cite this article as:
Marginal Vitamin A Deficiency Exacerbates Memory Deficits Following Aβ1-42 Injection in Rats, Current Alzheimer Research 2017; 14 (5) . https://dx.doi.org/10.2174/1567205013666161223162110
DOI https://dx.doi.org/10.2174/1567205013666161223162110 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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