Multigenerational effects of fetal-neonatal iron deficiency on hippocampal BDNF signaling
Article first published online: 2 OCT 2013
© 2013 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 1, Issue 5, October 2013
How to Cite
Physiol Rep, 1 (5), 2013, e00096, doi: 10.1002/phy2.96
- Issue published online: 23 SEP 2013
- Article first published online: 2 OCT 2013
- Manuscript Accepted: 29 AUG 2013
- Manuscript Received: 21 AUG 2013
- National Institutes of Health. Grant Number: 2R01 HD029421-17
Fetal-neonatal iron deficiency induces adult learning impairments concomitant with changes in expression of key genes underlying hippocampal learning and memory in spite of neonatal iron replenishment. Notably, expression of brain-derived neurotrophic factor (BDNF), a gene critical for neuronal maturation and synaptic plasticity, is lowered both acutely and in adulthood following early-life iron deficiency. Although the mechanism behind its long-term downregulation remains unclear, epigenetic modification in BDNF, as seen in other models of early-life adversity, may play a role. Given that early iron deficiency occurs during critical periods in both hippocampal and gonadal development, we hypothesized that the iron-sufficient offspring (F2 IS) of formerly iron-deficient (F1 FID) rats would show a similar suppression of the BDNF gene as their parents. We compared hippocampal mRNA levels of BDNF and functionally related genes among F1 IS, F1 ID, and F2 IS male rats at postnatal day (P) 15 and P65 using RT-qPCR. As expected, the F1 ID group showed a downregulation of BDNF and associated genes acutely at P15 and chronically at P65. However, the F2 IS group showed an upregulation of these genes at P15, returning to control levels at P65. These results demonstrate that adverse effects of early iron deficiency on hippocampal gene expression observed in the F1 are not present in the F2 generation, suggesting differential effects of nutritionally induced epigenetic programing during the critical periods of hippocampal and gonadal development.