Nizari Shereen, Carare Roxana O, Hawkes Cheryl A
Dept. of Life, Health and Chemical Sciences, Faculty of Science, Open University, Walton Hall, Milton Keynes, UK.
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
Sci Rep. 2016 Feb 25;6:21981. doi: 10.1038/srep21981.
Maternal obesity is associated with increased risk of developing diabetes, obesity and premature death in adult offspring. Mid-life diabetes, hypertension and hypercholesterolaemia are risk factors for the development of sporadic Alzheimer's disease (AD). A key pathogenic feature of AD is the accumulation of β-amyloid (Aβ) in the brain. The purpose of this study was to investigate the effect of high fat diet feeding during early life on Aβ pathology in the Tg2576 mouse model of AD. Female mice were fed a standard (C) or high fat (HF) diet before mating and during gestation and lactation. At weaning, male offspring were fed a C diet. Significantly higher levels of guanidine-soluble Aβ and plaque loads were observed in the hippocampi of 11-month old Tg2576 mice born to mothers fed a HF diet. Changes in the extracellular matrix led to increased retention of Aβ within the parenchyma. These data support a role for maternal and gestational health on the health of the aged brain and pathologies associated with AD and may provide a novel target for both the prevention and treatment of AD.
母体肥胖与成年后代患糖尿病、肥胖症和过早死亡的风险增加有关。中年糖尿病、高血压和高胆固醇血症是散发性阿尔茨海默病（AD）发病的危险因素。AD的一个关键致病特征是大脑中β-淀粉样蛋白（Aβ）的积累。本研究的目的是探讨生命早期高脂饮食对AD转基因小鼠模型（Tg2576）中Aβ病理的影响。雌性小鼠在交配前以及妊娠和哺乳期喂食标准（C）或高脂（HF）饮食。断奶时，雄性后代喂食C饮食。在喂食HF饮食的母亲所生的11个月大Tg2576小鼠的海马体中，观察到胍溶性Aβ水平和斑块负荷显著更高。细胞外基质的变化导致实质内Aβ的潴留增加。这些数据支持母体和孕期健康对老年大脑健康以及与AD相关的病理状况的作用，并可能为AD的预防和治疗提供新的靶点。
