Zeng Jiaying, Li Tingyu, Gong Ming, Jiang Wei, Yang Ting, Chen Jie, Liu Youxue, Chen Li
Children's Nutrition Research Center, Children's Hospital of Chongqing Medical University, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base for Child Development and Critical Disorders, Chongqing 400014, China.
Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children's Hospital of Chongqing Medical University, Chongqing 400014, China.
Curr Alzheimer Res. 2017;14(5):562-570. doi: 10.2174/1567205013666161223162110.
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.
The goal of this study was to investigate the long-term effects of MVAD on the pathogenesis of AD in rats.
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.
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.
Our study suggests that MVAD beginning from the embryonic period perturbs the ADassociated genes, resulting in an enhanced risk of developing AD.
尽管临床维生素A缺乏症（VAD）这一全球性的公共卫生问题已得到很好的控制，但边缘性维生素A缺乏症（MVAD）却更为普遍，尤其是在中国的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，生命早期开始的MVAD是否会增加患AD的风险尚未确定。
本研究的目的是探讨MVAD对大鼠AD发病机制的长期影响。
从母体MVAD大鼠建立MVAD模型，并在断奶后用MVAD饮食维持。雄性大鼠双侧海马CA3区注射聚集的淀粉样β蛋白（Aβ）1-42，检测与AD相关的认知和神经病理表型。
我们发现，在莫里斯水迷宫试验中，MVAD喂养显著加重了Aβ1-42诱导的学习和记忆缺陷。MVAD并未诱导Aβ1-42注射大鼠中视黄酸受体（RARs）、解整合素和金属蛋白酶10（ADAM10）或胰岛素降解酶（IDE）的mRNA表达。此外，RARα和RARγ mRNA与ADAM10 mRNA呈正相关，而RARβ mRNA与IDE mRNA呈正相关。
我们的研究表明，从胚胎期开始的MVAD会扰乱与AD相关的基因，从而增加患AD的风险。
