TY - JOUR
T1 - Long-term reduction of hippocampal brain-derived neurotrophic factor activity after fetal-neonatal iron deficiency in adult rats
AU - Tran, Phu V.
AU - Fretham, Stephanie J.B.
AU - Carlson, Erik S.
AU - Georgieff, Michael K.
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2009/5
Y1 - 2009/5
N2 - Fetal-neonatal iron deficiency acutely alters hippocampal biochemistry, neural morphology, and electrophysiology accompanied by a downregulation of brain-derived neurotrophic factor (BDNF). These changes provide a cellular and molecular basis for observed short-term learning and memory impairments. However, the etiology of residual, long-term hippocampal neurotransmission abnormalities and learning impairments after treatment remain unclear. Because BDNF modulates learning and memory, we assessed its expression in 65-d-old formerly iron deficient (FID) male rats that had been iron deficient during the fetal-neonatal period and treated with iron since postnatal day 7. BDNF-III and -IV mRNAs and BDNF protein expression remained down-regulated in FID rats when compared with the always iron-sufficient rats. Expressions of BDNF activity-dependent downstream targets (3-hydroxy-3-methylglutaryl CoA reductase and immediate early genes c-fos, early growth response gene 1 and 2) were reduced in FID rats. In turn, hippocampal expressions of direct targets of early-growth response genes, including hypoxia-inducible factor 1, dual-specificity phosphatase 4, IGF 2, and myelin basic protein were also diminished in FID rats. Collectively, fetal-neonatal iron deficiency lowers hippocampal BDNF expression and function beyond the period of iron deficiency. These findings may underlie the persistence of learning deficits seen after fetal-neonatal iron deficiency.
AB - Fetal-neonatal iron deficiency acutely alters hippocampal biochemistry, neural morphology, and electrophysiology accompanied by a downregulation of brain-derived neurotrophic factor (BDNF). These changes provide a cellular and molecular basis for observed short-term learning and memory impairments. However, the etiology of residual, long-term hippocampal neurotransmission abnormalities and learning impairments after treatment remain unclear. Because BDNF modulates learning and memory, we assessed its expression in 65-d-old formerly iron deficient (FID) male rats that had been iron deficient during the fetal-neonatal period and treated with iron since postnatal day 7. BDNF-III and -IV mRNAs and BDNF protein expression remained down-regulated in FID rats when compared with the always iron-sufficient rats. Expressions of BDNF activity-dependent downstream targets (3-hydroxy-3-methylglutaryl CoA reductase and immediate early genes c-fos, early growth response gene 1 and 2) were reduced in FID rats. In turn, hippocampal expressions of direct targets of early-growth response genes, including hypoxia-inducible factor 1, dual-specificity phosphatase 4, IGF 2, and myelin basic protein were also diminished in FID rats. Collectively, fetal-neonatal iron deficiency lowers hippocampal BDNF expression and function beyond the period of iron deficiency. These findings may underlie the persistence of learning deficits seen after fetal-neonatal iron deficiency.
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U2 - 10.1203/PDR.0b013e31819d90a1
DO - 10.1203/PDR.0b013e31819d90a1
M3 - Article
C2 - 19190544
AN - SCOPUS:69049085562
VL - 65
SP - 493
EP - 498
JO - Pediatric Research
JF - Pediatric Research
SN - 0031-3998
IS - 5
ER -