Long-Term Reduction of Hippocampal Brain-Derived Neurotrophic Factor Activity After Fetal-Neonatal Iron Deficiency in Adult Rats
| Autor: | Michael K. Georgieff, Erik S. Carlson, Stephanie J. B. Fretham, Phu V. Tran |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Brain-derived neurotrophic factor
medicine.medical_specialty biology Hippocampus Iron deficiency Hippocampal formation medicine.disease Myelin basic protein Endocrinology Downregulation and upregulation Iron-deficiency anemia Neurotrophic factors Internal medicine Pediatrics Perinatology and Child Health medicine biology.protein |
| Zdroj: | Pediatric Research. 65:493-498 |
| ISSN: | 1530-0447 0031-3998 |
| DOI: | 10.1203/pdr.0b013e31819d90a1 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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