Prenatal Malnutrition and the Aging Brain

产前营养不良和大脑老化

• 批准号: 7140525
• 负责人: Victoria L Herrera
• 金额: $ 16.76万
• 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 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7140525
• 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）： 在老年人口中，有许多人出现认知问题。随着老年人口的不断增加，迫切需要确定是否存在任何诱发因素。各种流行病学和动物实验工作的证据表明，出生时体型较小的个体（主要是由于产前营养不良所致）很容易在以后的生活中出现各种健康问题，例如心脏病、高血压、糖尿病等。这个过程被称为“产前编程”。然而，尚未研究产前营养不良/营养不良是否会使个体在衰老过程中容易出现认知功能障碍。这是当前项目的总体目标，并将利用完善的产前营养不良啮齿动物模型。众所周知，老年大鼠的亚群在涉及海马体和额叶皮层的任务中会出现行为表现缺陷。据推测，产前营养不良将使大鼠在衰老过程中容易出现认知功能障碍，因为已经有迹象表明，与成年早期额皮质功能障碍一致的行为变化，以及海马结构和功能的显着改变。使用横断面设计（使用同窝同伴），产前营养不良和营养良好的大鼠将在莫里斯水迷宫（海马体）中进行测试，并进行注意力转移任务，包括简单和复合辨别、维度内和维度外转移（内侧前额叶皮层） ）和逆转（眶额皮质），在 12、18、24 和 30 个月龄时。该项目很重要，因为经历过经济大萧条的人们遭受了许多贫困，包括营养不足。这些人现在正处于出现认知问题的黄金年龄。如果可以确定低出生体重会使个体在老年时认知能力下降更严重，那么就有可能制定治疗策略来预防或延缓被认定为“出生体重较小”的个体的认知能力下降。