Grant Abstract: Iron nutrition and impaired hippocampal development

Grant Number: 5R01HD050423-02
Project Title: Iron nutrition and impaired hippocampal development

Abstract: 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.

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