Martin Sarah A L, Jameson Christine H, Allan Stuart M, Lawrence Catherine B
Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
PLoS One. 2014 Jun 11;9(6):e99226. doi: 10.1371/journal.pone.0099226. eCollection 2014.
Alzheimer's disease (AD) is not normally diagnosed until later in life, although evidence suggests that the disease starts at a much earlier age. Risk factors for AD, such as diabetes, hypertension and obesity, are known to have their affects during mid-life, though events very early in life, including maternal over-nutrition, can predispose offspring to develop these conditions. This study tested whether over-nutrition during pregnancy and lactation affected the development of AD in offspring, using a transgenic AD mouse model. Female triple-transgenic AD dam mice (3xTgAD) were exposed to a high-fat (60% energy from fat) or control diet during pregnancy and lactation. After weaning (at 3 weeks of age), female offspring were placed on a control diet and monitored up until 12 months of age during which time behavioural tests were performed. A transient increase in body weight was observed in 4-week-old offspring 3xTgAD mice from dams fed a high-fat diet. However, by 5 weeks of age the body weight of 3xTgAD mice from the maternal high-fat fed group was no different when compared to control-fed mice. A maternal high-fat diet led to a significant impairment in memory in 2- and 12-month-old 3xTgAD offspring mice when compared to offspring from control fed dams. These effects of a maternal high-fat diet on memory were accompanied by a significant increase (50%) in the number of tau positive neurones in the hippocampus. These data demonstrate that a high-fat diet during pregnancy and lactation increases memory impairments in female 3xTgAD mice and suggest that early life events during development might influence the onset and progression of AD later in life.
阿尔茨海默病（AD）通常直到晚年才被诊断出来，尽管有证据表明该疾病在更早的年龄就已开始。已知AD的风险因素，如糖尿病、高血压和肥胖，在中年时期会产生影响，不过生命早期的一些事件，包括母体营养过剩，会使后代易患这些疾病。本研究使用转基因AD小鼠模型，测试了孕期和哺乳期营养过剩是否会影响后代AD的发展。雌性三转基因AD母鼠（3xTgAD）在孕期和哺乳期分别喂食高脂肪（脂肪提供60%能量）或对照饮食。断奶后（3周龄），雌性后代改为喂食对照饮食，并监测至12个月龄，在此期间进行行为测试。喂食高脂肪饮食的母鼠所产4周龄3xTgAD后代小鼠体重出现短暂增加。然而，到5周龄时，母体高脂肪喂养组的3xTgAD小鼠体重与对照喂养小鼠相比并无差异。与对照喂养母鼠所产后代相比，母体高脂肪饮食导致2个月龄和12个月龄的3xTgAD后代小鼠记忆显著受损。母体高脂肪饮食对记忆的这些影响伴随着海马体中tau阳性神经元数量显著增加（50%）。这些数据表明，孕期和哺乳期的高脂肪饮食会增加雌性3xTgAD小鼠的记忆损伤，并表明发育过程中的早期生命事件可能会影响晚年AD的发病和进展。
