Iron deficiency, hippocampal development, and learning

缺铁、海马发育和学习

• 批准号: 6789366
• 负责人: Matthew David McEchron
• 金额: $ 14.97万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-11 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6789366
• 关键词: behavioral /social science research tag; cognition disorders; conditioning; developmental disease /disorder; developmental neurobiology; developmental nutrition; dietary iron; fear; hippocampus; infant animal; laboratory rat; learning; learning disorders; malnutrition; mature animal; neurogenesis; nutrition related tag; synapses

DESCRIPTION (provided by applicant): The goal of this project is to identify the neural mechanisms involved in the well-established link between dietary iron deficiency (ID) and developmental impairments in learning and cognition. The hippocampus is the most important learning and memory structure in the mammalian brain. The hippocampus is critical for learning tasks that require the association of complex sets of information, and in humans it is critical for cognitive performance. Numerous studies in animals have shown that the hippocampus is more susceptible to ID during early development compared to other brain regions. An extensive list of animal and human studies has shown that ID impairs the development of learning and cognitive ability, and some of these studies suggest that these learning impairments persist well into adulthood. Together these lines of evidence strongly suggest that dietary ID alters the development of the hippocampus, and these alterations in turn significantly impact the development of children's cognitive and learning ability. Very little is known about how the functional physiology of the hippocampus is affected by ID during development. Experiment 1 in this proposal will determine if ID in postnatal developing rats impairs hippocampal synaptic responsiveness. This experiment will also determine if these physiological impairments are related to deficits in hippocampus-dependent learning. The animal learning paradigm that will be used in all of the experiments in this proposal combines trace and contextual fear conditioning, both of which have been shown to be dependent on the hippocampus. Our preliminary data demonstrate that ID in developing postnatal rats impairs learning in both of these hippocampus-dependent tasks. Our previous studies in normal adult animals have shown that single neurons in the hippocampus exhibit learning-specific encoding of the trace interval duration. Experiment 2 in this proposal will determine if ID in postnatal developing rats impairs hippocampal single neuron encoding of the trace interval duration during trace fear conditioning. Experiment 3 will determine if ID during postnatal development produces long-term impairments in hippocampal neurogenesis and hippocampus-dependent learning in young adult rats.

描述（由申请人提供）：该项目的目的是确定饮食铁缺乏症（ID）与学习和认知的发展障碍之间涉及的神经机制。海马是哺乳动物大脑中最重要的学习和记忆结构。海马对于需要复杂信息集合的学习任务至关重要，在人类中，这对于认知表现至关重要。对动物的许多研究表明，与其他大脑区域相比，海马在早期发育过程中更容易受到ID的影响。大量的动物和人类研究清单表明，ID会损害学习和认知能力的发展，其中一些研究表明，这些学习障碍一直持续到成年。这些证据共同表明，饮食ID会改变海马的发展，而这些变化反过来又影响了儿童认知和学习能力的发展。关于海马的功能生理如何受到发育过程中ID的影响，知之甚少。 该提案中的实验1将确定产后发育中的大鼠中的ID是否会损害海马突触反应能力。该实验还将确定这些生理障碍是否与海马依赖性学习的缺陷有关。该提案中所有实验中都将使用的动物学习范式结合了痕量和上下文恐惧调节，这两者都依赖于海马。我们的初步数据表明，发展产后大鼠的ID会损害这两个海马依赖性任务中的学习。我们先前对正常成年动物的研究表明，海马中的单个神经元表现出对痕量间隔持续时间的学习特异性编码。实验2在此提案中将确定产后发育中的大鼠中的ID是否会损害痕量恐惧调节过程中痕量间隔持续时间的海马单神经元编码。实验3将确定产后发育过程中的ID是否会导致年轻大鼠海马神经发生和海马依赖性学习的长期障碍。