Neonatal mouse hippocampus: Phlebotomy-induced anemia diminishes and treatment with erythropoietin partially rescues mammalian target of rapamycin (mTOR) signaling
| Autor: | Phu V. Tran, Diana Wallin, Michelle Alexander, Tara G Zamora, Kathleen Ennis, Michael K. Georgieff |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
medicine.medical_specialty
Anemia Hippocampus Article 03 medical and health sciences Mice 0302 clinical medicine Phlebotomy Pregnancy hemic and lymphatic diseases 030225 pediatrics Internal medicine medicine Animals Erythropoietin 2. Zero hunger business.industry Pediatric research TOR Serine-Threonine Kinases Neonatal mouse medicine.disease Mice Inbred C57BL Endocrinology Animals Newborn Pediatrics Perinatology and Child Health Female business 030217 neurology & neurosurgery medicine.drug Signal Transduction |
| Zdroj: | Pediatric research |
| ISSN: | 1530-0447 0031-3998 |
| Popis: | BackgroundPhlebotomy-induced anemia (PIA) is common in premature infants and affects neurodevelopment. PIA alters hippocampal metabolism in neonatal mice through tissue hypoxia and iron deficiency. The mammalian target of rapamycin (mTOR) pathway senses the status of critical metabolites (e.g., oxygen, iron), thereby regulating hippocampal growth and function. We determined the effect of PIA and recombinant human erythropoietin (rHuEpo) treatment on mTOR signaling and expression of genes related to mTOR pathway functions.MethodsMice receiving an iron-supplemented diet were phlebotomized from postnatal day (P)3 to a target hematocrit of25% by P7. Half were maintained at25% until P14; half received rHuEpo from P7 to increase the hematocrit to 25-28%. Hippocampal phosphorylated to total protein ratios of four key mTOR pathway proteins were measured by western blotting at P14 and compared with non-phlebotomized, non-anemic control mice. mRNA levels of genes regulated by mTOR were measured by quantitative PCR.ResultsPIA suppressed phosphorylation of all mTOR proteins. rHuEpo restored AMP-activated protein kinase (AMPK) and AKT status, and partially rescued the mTOR output protein S6K. PIA and rHuEpo treatment also altered the expression of genes regulated by S6K.ConclusionPIA compromises and rHuEpo treatment partially rescues a pathway regulating neuronal DNA transcription, protein translation, and structural complexity. |
| Databáze: | OpenAIRE |
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