Toxicity Assessment Division, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA.
Neurotoxicol Teratol. 2010 May-Jun;32(3):362-72. doi: 10.1016/j.ntt.2009.12.008. Epub 2009 Dec 31.
Low weight at birth is a common adverse developmental effect reported in human populations and animal toxicity studies. Epidemiological evidence links low birth weight to a syndrome of metabolic changes that increase later risk for obesity, type 2 diabetes, hypertension, and cardiovascular disease. The present study used a four-treatment cross-over experimental design to evaluate the selective impact of early nutritional deficiency on metabolism and brain function across the lifespan of male Sprague Dawley rats. Undernutrition was induced prenatally by restricting maternal food intake to 50% of ad lib from GD3 to birth. Postnatal undernutrition was induced by fostering pups at birth to naïve dams in large (n=16) litters as opposed to small (n=8) control litters. Body weights were monitored in the early neonatal period, in early adulthood beginning at 5months and through to senescence at 21months of age. In contrast to recent reports, no increase in the prevalence of obesity was seen in animals born to food restricted dams and reared under ad lib feeding conditions. Behavioral tests of locomotion, learning and memory were performed in young, middle-aged, and aged animals. No effects of pre or postnatal nutritional history were detected. Age-dependent reductions in locomotor activity were detected, as well as deficits in spatial learning as measured in the Morris water maze and in context fear conditioning. These findings indicate that moderate fetal undernutrition followed by neonatal adequate nutrition does not appear to lead to obesity or neurological dysfunction in young adulthood or old age.
出生体重低是人类和动物毒性研究中常见的不良发育影响。流行病学证据表明,出生体重低与代谢变化综合征有关,这种综合征会增加肥胖、2 型糖尿病、高血压和心血管疾病的后期风险。本研究采用四处理交叉实验设计,评估早期营养缺乏对雄性 Sprague Dawley 大鼠整个生命周期代谢和大脑功能的选择性影响。孕期通过限制母体饮食摄入至 GD3 至出生时的 50%来诱导营养不足。产后营养不足通过将新生幼崽寄养在没有经验的母鼠大(n=16)窝中而不是小(n=8)对照组中诱导。在新生儿早期和 5 个月开始的成年早期以及 21 个月的衰老期监测体重。与最近的报道相反,在出生时由限制饮食的母鼠喂养并在自由喂养条件下饲养的动物中,肥胖的患病率没有增加。在年轻、中年和老年动物中进行了运动、学习和记忆的行为测试。未检测到产前或产后营养史的影响。检测到与年龄相关的运动活性降低,以及在 Morris 水迷宫和情境恐惧条件反射中测量的空间学习缺陷。这些发现表明,中度胎儿营养不足随后是新生儿充足营养,似乎不会导致成年期或老年期肥胖或神经功能障碍。