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Gestational Iron Deficiency disrupts neural patterning in the embryo

妊娠期缺铁会破坏胚胎的神经模式

基本信息

批准号：
10286844
负责人：
MARGOT MAYER-PROSCHEL
金额：
$ 37.42万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10286844
关键词：
Affect Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease model Alzheimer&apos s disease pathology Amyloid Animal Disease Models Animal Model Behavioral Behavioral Assay Birth Brain Cells Cognitive deficits Defect Deficiency Diseases Demyelinations Development Disease Disease Progression Embryo Environmental Risk Factor Equilibrium Exposure to Funding Goals Herpesviridae Human Hyperactivity Impaired cognition Impairment Infection Inflammation Interneurons Iron Latent virus infection phase Lead Learning Life Link Malnutrition Memory Metals Microtubules Modeling Mutation National Institute of Child Health and Human Development Neurites Neuronal Differentiation Neurons Parvalbumins Pathogenicity Pathologic Pathology Play Population Pregnancy Presenile Alzheimer Dementia Proteins Refractory Research Project Grants Role Senile Plaques Severities Severity of illness Signal Transduction Supplementation Synapses Testing Time Virus Diseases Work cellular pathology cognitive development early life exposure early onset familial Alzheimer disease in vivo iron deficiency iron supplementation mature animal mouse model neural patterning neuron loss novel offspring postnatal relating to nervous system tau Proteins

项目摘要

Abstract This supplemental funding request builds on our EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT-sponsored research grant that is focused on the impact of gestational iron deficiency (GID) on brain development. In the course of this work we have discovered that GID alters neuronal cell populations in the embryonic brain which result in an altered balance of excitatory and inhibitory signaling (E/I balance) later in life. This imbalance, which is associated with a decrease in parvalbumin expressing interneurons (PV) is refractory to postnatal iron supplementation suggesting that the changes that occur in the embryo are permanent and might render the brain vulnerable to other insults later in life. Interestingly, recent studies have found that Alzheimer disease is also associated with an impaired E/I balance and mouse models of Alzheimer disease show a significant reduction in the number of PV- expressing cells in the cortex compared with age-matched wild-type counterparts. These observations, together with our recent findings that GID causes region specific dysregulation of metals in the brain (which is also found in AD), raise the interesting hypothesis that gestational iron deficiency renders offspring more susceptible to Alzheimer disease later in life. We will test this novel hypothesis by establishing double-insult models where we expose animal models of familial AD to GID and test whether GID alters the time of onset of pathology and the severity of AD pathology. As a positive control, we will also combine AD mouse models with our newly generated mouse model of early-life exposure to latent human herpes virus 6 infections (HHV6), a secondary insult that has recently been linked to AD and has been suggested to be a pathology modulator.

摘要