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Fetal iron deficiency induces chromatin remodeling at the Bdnf locus in adult rat hippocampus.
- Source :
-
American journal of physiology. Regulatory, integrative and comparative physiology [Am J Physiol Regul Integr Comp Physiol] 2015 Feb 15; Vol. 308 (4), pp. R276-82. Date of Electronic Publication: 2014 Dec 17. - Publication Year :
- 2015
-
Abstract
- Fetal and subsequent early postnatal iron deficiency causes persistent impairments in cognitive and affective behaviors despite prompt postnatal iron repletion. The long-term cognitive impacts are accompanied by persistent downregulation of brain-derived neurotrophic factor (BDNF), a factor critical for hippocampal plasticity across the life span. This study determined whether early-life iron deficiency epigenetically modifies the Bdnf locus and whether dietary choline supplementation during late gestation reverses these modifications. DNA methylation and histone modifications were assessed at the Bdnf-IV promoter in the hippocampus of rats [at postnatal day (PND) 65] that were iron-deficient (ID) during the fetal-neonatal period. Iron deficiency was induced in rat pups by providing pregnant and nursing dams an ID diet (4 mg/kg Fe) from gestational day (G) 2 through PND7, after which iron deficiency was treated with an iron-sufficient (IS) diet (200 mg/kg Fe). This paradigm resulted in about 60% hippocampal iron loss on PND15 with complete recovery by PND65. For choline supplementation, pregnant rat dams were given dietary choline (5 g/kg) from G11 through G18. DNA methylation was determined by quantitative sequencing of bisulfite-treated DNA, revealing a small alteration at the Bdnf-IV promoter. Chromatin immunoprecipitation analysis showed increased HDAC1 binding accompanied by reduced binding of RNA polymerase II and USF1 at the Bdnf-IV promoter in formerly ID rats. These changes were correlated with altered histone methylations. Prenatal choline supplementation reverses these epigenetic modifications. Collectively, the findings identify epigenetic modifications as a potential mechanism to explicate the long-term repression of Bdnf following fetal and early postnatal iron deficiency.<br /> (Copyright © 2015 the American Physiological Society.)
- Subjects :
- Age Factors
Animals
Binding Sites
Brain-Derived Neurotrophic Factor metabolism
Choline administration & dosage
Disease Models, Animal
Down-Regulation
Female
Gestational Age
Hippocampus drug effects
Histone Deacetylase 1 metabolism
Histones metabolism
Iron blood
Iron Metabolism Disorders blood
Iron Metabolism Disorders complications
Iron Metabolism Disorders drug therapy
Methylation
Pregnancy
Promoter Regions, Genetic
RNA Polymerase II metabolism
Rats, Sprague-Dawley
Time Factors
Upstream Stimulatory Factors metabolism
Brain-Derived Neurotrophic Factor genetics
Chromatin Assembly and Disassembly drug effects
DNA Methylation drug effects
Epigenesis, Genetic drug effects
Hippocampus metabolism
Iron Deficiencies
Iron Metabolism Disorders genetics
Prenatal Exposure Delayed Effects
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1490
- Volume :
- 308
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Regulatory, integrative and comparative physiology
- Publication Type :
- Academic Journal
- Accession number :
- 25519736
- Full Text :
- https://doi.org/10.1152/ajpregu.00429.2014