Prenatal Malnutrition and the Aging Brain

产前营养不良和大脑老化

• 批准号: 6984328
• 负责人: JOHN TONKISS
• 金额: $ 20.59万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6984328
• 关键词: animal birth weight; animal old age; behavior prediction; behavior test; behavioral /social science research tag; brain morphology; cognition disorders; disease /disorder proneness /risk; frontal lobe /cortex; hippocampus; laboratory rat; malnutrition; mother /embryo /fetus nutrition; nutrition related tag; prenatal growth disorder

DESCRIPTION (provided by applicant): In the elderly population there are many who develop cognitive problems. As the aged population is increasing there is an urgent need to determine if there are any predisposing factors. Evidence from a variety of epidemiological and animal experimental work suggests that individuals who are born small (primarily resulting from prenatal undernutrition) are prone to develop a variety of health problems later in life, e.g., heart disease, hypertension, diabetes and more. A process that has been termed, "prenatal programming". However, whether prenatal undernutrition/malnutrition predisposes individuals to cognitive dysfunction during senescence has not been examined. This is the broad objective of the current project, and will take advantage of a well-established rodent model of prenatal malnutrition. Sub-populations of aged rats are known to develop deficient behavioral performance on tasks that involve the hippocampus and the frontal cortex. It is postulated that prenatal malnutrition will predispose rats to cognitive dysfunction during senescence since there are already indications of behavioral changes consistent with frontal cortical dysfunction in young adulthood, and significant alterations in the structure and function of the hippocampus. Using a cross sectional design (using litter mates) prenatally malnourished and well-nourished rats will be tested in the Morris water maze (hippocampus) and attentional set shifting tasks consisting of simple and compound discriminations, intra-dimensional and extradimensional shifts (medial prefrontal cortex) and in reversals (orbitofrontal cortex), at 12, 18, 24 and 30 months of age. This project is important because the population that lived through the great economic depression suffered many privations, including inadequate nutrition. These individuals are now of a prime age for developing cognitive problems. If it can be established that low birth weight predisposes individuals to greater cognitive decline in old age it may be possible to develop therapeutic strategies to forestall or retard the decline in individuals identified as being "born small."

描述（由申请人提供）： 在老年人中，有许多人出现认知问题。随着老年人口的增加，迫切需要确定是否存在任何诱发因素。来自各种流行病学和动物实验工作的证据表明，天生小的个体（主要是由于营养不良而导致的）容易发生后期生活中的各种健康问题，例如心脏病，高血压，糖尿病等。被称为“产前编程”的过程。但是，尚未检查产前营养不良/营养不良在衰老过程中易于认知功能障碍。这是当前项目的广泛目标，它将利用成熟的啮齿动物营养不良模型。已知衰老大鼠的亚群会在涉及海马和额叶皮层的任务上发展不足的行为表现。据推测，产前营养不良会使大鼠在衰老过程中诱发认知功能障碍，因为已经有迹象表明与成年年轻人的额叶皮质功能障碍一致，并且河马的结构和功能发生了重大变化。 Using a cross sectional design (using litter mates) prenatally malnourished and well-nourished rats will be tested in the Morris water maze (hippocampus) and attentional set shifting tasks consisting of simple and compound discriminations, intra-dimensional and extradimensional shifts (medial prefrontal cortex) and in reversals (orbitofrontal cortex), at 12, 18, 24 and 30几个月。该项目很重要，因为经济萧条生活的人口遭受了许多侵害，包括营养不足。这些人现在是发展认知问题的黄金年龄。如果可以确定，低出生体重会使个人在老年人的认知能力下降较大，则可能有可能制定治疗策略，以阻止或阻止被确定为“天生小”的个体的下降。