PMID- 28399115
OWN - NLM
STAT- MEDLINE
DCOM- 20180516
LR  - 20211204
IS  - 1530-0447 (Electronic)
IS  - 0031-3998 (Print)
IS  - 0031-3998 (Linking)
VI  - 82
IP  - 3
DP  - 2017 Sep
TI  - Neonatal mouse hippocampus: phlebotomy-induced anemia diminishes and treatment 
      with erythropoietin partially rescues mammalian target of rapamycin signaling.
PG  - 501-508
LID - 10.1038/pr.2017.88 [doi]
AB  - 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 of <25% by P7. Half were maintained at <25% 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.
FAU - Wallin, Diana J
AU  - Wallin DJ
AD  - Graduate Program in Neuroscience, Department of Neuroscience, University of 
      Minnesota, Minneapolis, Minnesota.
FAU - Zamora, Tara G
AU  - Zamora TG
AD  - Children's Hospitals and Clinics of Minnesota, St. Paul, Minnesota.
FAU - Alexander, Michelle
AU  - Alexander M
AD  - Division of Neonatology, Department of Pediatrics, University of Minnesota, 
      Minneapolis, Minnesota.
FAU - Ennis, Kathleen M
AU  - Ennis KM
AD  - Division of Neonatology, Department of Pediatrics, University of Minnesota, 
      Minneapolis, Minnesota.
FAU - Tran, Phu V
AU  - Tran PV
AD  - Division of Neonatology, Department of Pediatrics, University of Minnesota, 
      Minneapolis, Minnesota.
FAU - Georgieff, Michael K
AU  - Georgieff MK
AD  - Division of Neonatology, Department of Pediatrics, University of Minnesota, 
      Minneapolis, Minnesota.
LA  - eng
GR  - P01 HL046925/HL/NHLBI NIH HHS/United States
GR  - R01 HD029421/HD/NICHD NIH HHS/United States
GR  - T32 GM008471/GM/NIGMS NIH HHS/United States
GR  - UL1 TR000114/TR/NCATS NIH HHS/United States
PT  - Journal Article
DEP - 20170531
PL  - United States
TA  - Pediatr Res
JT  - Pediatric research
JID - 0100714
RN  - 11096-26-7 (Erythropoietin)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Anemia/*drug therapy/etiology
MH  - Animals
MH  - *Animals, Newborn
MH  - Erythropoietin/*administration & dosage/*therapeutic use
MH  - Female
MH  - Hippocampus/*pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Phlebotomy/*adverse effects
MH  - Pregnancy
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
PMC - PMC5570638
MID - NIHMS863443
COIS- The authors have no financial ties or conflicts of interest to disclose.
EDAT- 2017/04/12 06:00
MHDA- 2018/05/17 06:00
PMCR- 2017/11/30
CRDT- 2017/04/12 06:00
PHST- 2016/10/12 00:00 [received]
PHST- 2017/03/17 00:00 [accepted]
PHST- 2017/04/12 06:00 [pubmed]
PHST- 2018/05/17 06:00 [medline]
PHST- 2017/04/12 06:00 [entrez]
PHST- 2017/11/30 00:00 [pmc-release]
AID - pr201788 [pii]
AID - 10.1038/pr.2017.88 [doi]
PST - ppublish
SO  - Pediatr Res. 2017 Sep;82(3):501-508. doi: 10.1038/pr.2017.88. Epub 2017 May 31.