Iron nutrition and impaired hippocampal development

铁营养和海马发育受损

基本信息

批准号：
7882496
负责人：
Matthew David McEchron
金额：
$ 23.59万
依托单位：
UNIVERSITY OF WYOMING
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-15 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7882496
关键词：
Address Adult Affect Amygdaloid structure Animals Area Behavioral Biochemical Biochemistry Brain Cell physiology Child Cognition Cognitive Complex Development Diet Electrophysiology (science)Exhibits Ferritin Fiber Future Genetic Genetic Models H ferritin Hippocampus (Brain)Hour Human Immunoblotting Immunohistochemistry Impaired cognition Impairment In Vitro Iron Learning Measures Memory Modeling Mutant Strains Mice Myelin Neurons Nutrition Disorders Nutritional Other Genetics Performance Perinatal Physiological Prefrontal Cortex Preparation Process Protein Analysis Proteins Protocols documentation Rattus Reporting Research Personnel Retrieval Slice Stimulus Structure Synapses Synaptic Transmission Testing Time Training Transferrin Work age group behavior test density entorhinal cortex hippocampal subregions memory retention memory retrieval mouse model nutrition postnatal prevent programs research study response treatment strategy young adult

项目摘要

DESCRIPTION (provided by applicant): Developmental iron deficiency (ID) results in impaired learning and cognition in children (e.g., Lozoff et al., 2000). This suggests that the development of one or more cognitive-learning areas in the brain may be compromised by early nutritional ID. This is alarming because ID is the most prevalent nutritional disorder in the world, and several reports show that ID during development produces cognitive impairments that are irreversible. One brain area that is severely affected by developmental ID is the hippocampus. The hippocampus is required for the association of complex sets of information, and in humans it is critical for cognitive performance. One of our recently completed studies shows that perinatal nutritional ID in rats impairs synaptic transmission in multiple subregions of the hippocampus. Another of our completed studies shows that perinatal ID in rats impairs hippocampus-dependent learning, and these learning impairments last into adulthood and are not reversed by an iron sufficient diet. These and other studies suggest that perinatal ID impairs one or more cellular processes in the hippocampus resulting in permanent learning deficits. It is not known, however, which cellular or biochemical mechanisms in the hippocampus are irreversibly impaired by perinatal ID. It is also not known if other moderate forms of perinatal ID or other genetic models of reduced iron storage capacity result in similar deficits in learning ability and cellular function in the hippocampus. Aims I and II in this proposal will address these issues. Our synaptic transmission study shows that perinatal ID impairs synaptic efficacy in multiple regions of the hippocampus. This raises the possibility that perinatal ID impairs synaptic transmission in many other learning centers outside of the hippocampus. Aim III will determine if important learning and memory centers in close proximity to the hippocampus and others far removed from the hippocampus show similar deficits in synaptic transmission. Our learning study and the work of others shows that perinatal nutritional ID impairs learning ability in animals and children. Aim IV will determine if these learning deficits can be overcome by strengthening the acquisition of information or reducing the memory retention interval. Moreover, these aims provide a comprehensive strategy for 1, identifying the neuroanatomical and cellular mechanisms permanently impacted by developmental ID; 2, determining the relationship of these mechanisms to impaired cognitive development; and 3, determining if some cognitive impairments can be reversed by manipulating the learning process.

描述（由申请人提供）：发育铁缺乏症（ID）导致儿童学习和认知受损（例如Lozoff等，2000）。这表明大脑中一个或多个认知学习区域的发展可能会因早期营养ID而受到损害。这是令人震惊的，因为ID是世界上最普遍的营养障碍，并且有几份报告表明，发育过程中的ID会产生不可逆的认知障碍。海马是一个受发育ID严重影响的大脑区域。海马是复杂信息集合所必需的，在人类中，这对于认知表现至关重要。我们最近完成的一项研究表明，大鼠的围产期营养ID会损害海马多个子区域的突触传播。我们完成的另一项研究表明，大鼠的围产期ID会损害海马依赖性学习，而这些学习障碍持续到成年，并且不会被铁足够的饮食逆转。这些和其他研究表明，围产期ID会损害海马中的一个或多个细胞过程，从而导致永久性学习缺陷。然而，尚不清楚海马中哪种细胞或生化机制会因围产期ID不可逆转地损害。还不知道其他中等形式的围产期ID或其他降低铁储存能力的遗传模型是否会导致海马中的学习能力和细胞功能相似。目的I和II在此提案中将解决这些问题。我们的突触传播研究表明，围产期ID会损害海马多个区域的突触功效。这增加了围产期ID会损害海马以外许多其他学习中心的突触传播的可能性。 AIM III将确定重要的学习和记忆中心是否与海马以及与海马远离海马的其他距离密切相似，在突触传播中显示出相似的缺陷。我们的学习研究和其他工作表明，围产期营养ID会损害动物和儿童的学习能力。 AIM IV将通过加强信息的获取或减少记忆保持间隔来确定这些学习缺陷是否可以克服。此外，这些目标为1提供了全面的策略，确定了受发育ID永久影响的神经解剖学和细胞机制； 2，确定这些机制与认知发展损害的关系； 3，确定是否可以通过操纵学习过程来逆转某些认知障碍。