TY - JOUR
T1 - Early-life iron deficiency anemia alters neurotrophic factor expression and hippocampal neuron differentiation in male rats
AU - Tran, Phu V.
AU - Carlson, Erik S.
AU - Fretham, Stephanie J.B.
AU - Georgieff, Michael K.
PY - 2008/12
Y1 - 2008/12
N2 - Fetal-neonatal iron deficiency alters hippocampal neuronal morphology, reduces its volume, and is associated with acute and long-term learning impairments. However, neither the effects of early-life iron deficiency anemia on growth, differentiation, and survival of hippocampal neurons nor regulation of the neurotrophic factors that mediate these processes has been investigated. We compared hippocampal expression of neurotrophic factors in male rats made iron deficient (ID) from gestational d 2 to postnatal d (P) 7 to iron-sufficient controls at P7, 15, and 30 with quantitative RT-PCR, Western analysis, and immunohistology. Iron deficiency downregulated brain-derived neurotrophic factor (BDNF) expression in the hippocampus without compensatory upregulation of its specific receptor, tyrosine-receptor kinase B. Consistent with low overall BDNF activity, we found lower expression of early-growth response gene-1 and -2, transcriptional targets of BDNF signaling. Doublecortin expression, a marker of differentiating neurons,was reduced during peak iron deficiency, suggesting impaired neuronal differentiation in the ID hippocampus. In contrast, iron deficiency upregulated hippocampal nerve growth factor, epidermal growth factor, and glial-derived neurotrophic factor accompanied by an increase in neurotrophic receptor p75 expression. Our findings suggest that fetal-neonatal iron deficiency lowers BDNF function and impairs neuronal differentiation in the hippocampus.
AB - Fetal-neonatal iron deficiency alters hippocampal neuronal morphology, reduces its volume, and is associated with acute and long-term learning impairments. However, neither the effects of early-life iron deficiency anemia on growth, differentiation, and survival of hippocampal neurons nor regulation of the neurotrophic factors that mediate these processes has been investigated. We compared hippocampal expression of neurotrophic factors in male rats made iron deficient (ID) from gestational d 2 to postnatal d (P) 7 to iron-sufficient controls at P7, 15, and 30 with quantitative RT-PCR, Western analysis, and immunohistology. Iron deficiency downregulated brain-derived neurotrophic factor (BDNF) expression in the hippocampus without compensatory upregulation of its specific receptor, tyrosine-receptor kinase B. Consistent with low overall BDNF activity, we found lower expression of early-growth response gene-1 and -2, transcriptional targets of BDNF signaling. Doublecortin expression, a marker of differentiating neurons,was reduced during peak iron deficiency, suggesting impaired neuronal differentiation in the ID hippocampus. In contrast, iron deficiency upregulated hippocampal nerve growth factor, epidermal growth factor, and glial-derived neurotrophic factor accompanied by an increase in neurotrophic receptor p75 expression. Our findings suggest that fetal-neonatal iron deficiency lowers BDNF function and impairs neuronal differentiation in the hippocampus.
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U2 - 10.3945/jn.108.091553
DO - 10.3945/jn.108.091553
M3 - Article
C2 - 19022978
AN - SCOPUS:57349165847
SN - 0022-3166
VL - 138
SP - 2495
EP - 2501
JO - Journal of Nutrition
JF - Journal of Nutrition
IS - 12
ER -