Neonatal mouse hippocampus: phlebotomy-induced anemia diminishes and treatment with erythropoietin partially rescues mammalian target of rapamycin signaling
Background Phlebotomy-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., oxy...
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| Veröffentlicht in: | Pediatric research 2017-09, Vol.82 (3), p.501-508 |
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| creator | Wallin, Diana J Zamora, Tara G Alexander, Michelle Ennis, Kathleen M Tran, Phu V Georgieff, Michael K |
| description | Background
Phlebotomy-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.
Methods
Mice receiving an iron-supplemented diet were phlebotomized from postnatal day (P)3 to a target hematocrit of |
| doi_str_mv | 10.1038/pr.2017.88 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5570638</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1931681776</sourcerecordid><originalsourceid>FETCH-LOGICAL-c442t-1d4e36695ad526c8c2084c3f449fba40ef51dea0a215811b0661468e984d4b613</originalsourceid><addsrcrecordid>eNplkU2L1TAUhoMoznV04w-QgBtRek3atE1nIcjgFwy60XU4TU9vMzRJTVKl_8Ufay53HEZdhXPeJ-_5IuQpZ3vOKvl6CfuS8XYv5T2y43XFCiZEe5_sGKt4UXWdPCOPYrxmjItaiofkrJQ5y3m9I78-o3eQYKbWrxHpZJbFa7DLGi_oMs3Y--TtVhg3rBoHCg6tAToYa5yJE8acGWgKCMmiS_SnSRPFsKUp-MUbTMbRBUIyMM8bDRj1mv9YsBZmA44mCAdM1I80wAJ205mP5uCy6g6PyYMR5ohPbt5z8u39u6-XH4urLx8-Xb69KrQQZSr4ILBqmq6GoS4bLXXJpNDVKEQ39iAYjjUfEBiUvJac96xpuGgkdlIMom94dU7enHyXtbc46DxIgFktwVgIm_Jg1N-KM5M6-B-qrlvWVDIbvLgxCP57HjApa6LGec7rymtVXMqW5d54ldHn_6DXfg153kx1FW8kb9smUy9PlA4-xoDjbTOcqePRc6yOR1fyWP3Z3fZv0T9XzsCrExCz5A4Y7tT83-43fqe7HQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1931681776</pqid></control><display><type>article</type><title>Neonatal mouse hippocampus: phlebotomy-induced anemia diminishes and treatment with erythropoietin partially rescues mammalian target of rapamycin signaling</title><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Wallin, Diana J ; Zamora, Tara G ; Alexander, Michelle ; Ennis, Kathleen M ; Tran, Phu V ; Georgieff, Michael K</creator><creatorcontrib>Wallin, Diana J ; Zamora, Tara G ; Alexander, Michelle ; Ennis, Kathleen M ; Tran, Phu V ; Georgieff, Michael K</creatorcontrib><description>Background
Phlebotomy-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.
Methods
Mice 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.
Results
PIA 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.
Conclusion
PIA compromises and rHuEpo treatment partially rescues a pathway regulating neuronal DNA transcription, protein translation, and structural complexity.</description><identifier>ISSN: 0031-3998</identifier><identifier>EISSN: 1530-0447</identifier><identifier>DOI: 10.1038/pr.2017.88</identifier><identifier>PMID: 28399115</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/61/51/2314 ; 631/80/83/2359 ; 692/699/1541/13 ; 692/700/1720/3186 ; Anemia ; Iron ; Kinases ; Medicine ; Medicine & Public Health ; Neurology ; Pediatric Surgery ; Pediatrics ; Premature birth ; Proteins ; Rodents ; translational-investigation</subject><ispartof>Pediatric research, 2017-09, Vol.82 (3), p.501-508</ispartof><rights>International Pediatric Research Foundation, Inc. 2017</rights><rights>Copyright Nature Publishing Group Sep 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c442t-1d4e36695ad526c8c2084c3f449fba40ef51dea0a215811b0661468e984d4b613</citedby><cites>FETCH-LOGICAL-c442t-1d4e36695ad526c8c2084c3f449fba40ef51dea0a215811b0661468e984d4b613</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28399115$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wallin, Diana J</creatorcontrib><creatorcontrib>Zamora, Tara G</creatorcontrib><creatorcontrib>Alexander, Michelle</creatorcontrib><creatorcontrib>Ennis, Kathleen M</creatorcontrib><creatorcontrib>Tran, Phu V</creatorcontrib><creatorcontrib>Georgieff, Michael K</creatorcontrib><title>Neonatal mouse hippocampus: phlebotomy-induced anemia diminishes and treatment with erythropoietin partially rescues mammalian target of rapamycin signaling</title><title>Pediatric research</title><addtitle>Pediatr Res</addtitle><addtitle>Pediatr Res</addtitle><description>Background
Phlebotomy-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.
Methods
Mice 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.
Results
PIA 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.
Conclusion
PIA compromises and rHuEpo treatment partially rescues a pathway regulating neuronal DNA transcription, protein translation, and structural complexity.</description><subject>631/61/51/2314</subject><subject>631/80/83/2359</subject><subject>692/699/1541/13</subject><subject>692/700/1720/3186</subject><subject>Anemia</subject><subject>Iron</subject><subject>Kinases</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Neurology</subject><subject>Pediatric Surgery</subject><subject>Pediatrics</subject><subject>Premature birth</subject><subject>Proteins</subject><subject>Rodents</subject><subject>translational-investigation</subject><issn>0031-3998</issn><issn>1530-0447</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNplkU2L1TAUhoMoznV04w-QgBtRek3atE1nIcjgFwy60XU4TU9vMzRJTVKl_8Ufay53HEZdhXPeJ-_5IuQpZ3vOKvl6CfuS8XYv5T2y43XFCiZEe5_sGKt4UXWdPCOPYrxmjItaiofkrJQ5y3m9I78-o3eQYKbWrxHpZJbFa7DLGi_oMs3Y--TtVhg3rBoHCg6tAToYa5yJE8acGWgKCMmiS_SnSRPFsKUp-MUbTMbRBUIyMM8bDRj1mv9YsBZmA44mCAdM1I80wAJ205mP5uCy6g6PyYMR5ohPbt5z8u39u6-XH4urLx8-Xb69KrQQZSr4ILBqmq6GoS4bLXXJpNDVKEQ39iAYjjUfEBiUvJac96xpuGgkdlIMom94dU7enHyXtbc46DxIgFktwVgIm_Jg1N-KM5M6-B-qrlvWVDIbvLgxCP57HjApa6LGec7rymtVXMqW5d54ldHn_6DXfg153kx1FW8kb9smUy9PlA4-xoDjbTOcqePRc6yOR1fyWP3Z3fZv0T9XzsCrExCz5A4Y7tT83-43fqe7HQ</recordid><startdate>20170901</startdate><enddate>20170901</enddate><creator>Wallin, Diana J</creator><creator>Zamora, Tara G</creator><creator>Alexander, Michelle</creator><creator>Ennis, Kathleen M</creator><creator>Tran, Phu V</creator><creator>Georgieff, Michael K</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170901</creationdate><title>Neonatal mouse hippocampus: phlebotomy-induced anemia diminishes and treatment with erythropoietin partially rescues mammalian target of rapamycin signaling</title><author>Wallin, Diana J ; Zamora, Tara G ; Alexander, Michelle ; Ennis, Kathleen M ; Tran, Phu V ; Georgieff, Michael K</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c442t-1d4e36695ad526c8c2084c3f449fba40ef51dea0a215811b0661468e984d4b613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>631/61/51/2314</topic><topic>631/80/83/2359</topic><topic>692/699/1541/13</topic><topic>692/700/1720/3186</topic><topic>Anemia</topic><topic>Iron</topic><topic>Kinases</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Neurology</topic><topic>Pediatric Surgery</topic><topic>Pediatrics</topic><topic>Premature birth</topic><topic>Proteins</topic><topic>Rodents</topic><topic>translational-investigation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wallin, Diana J</creatorcontrib><creatorcontrib>Zamora, Tara G</creatorcontrib><creatorcontrib>Alexander, Michelle</creatorcontrib><creatorcontrib>Ennis, Kathleen M</creatorcontrib><creatorcontrib>Tran, Phu V</creatorcontrib><creatorcontrib>Georgieff, Michael K</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Pediatric research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wallin, Diana J</au><au>Zamora, Tara G</au><au>Alexander, Michelle</au><au>Ennis, Kathleen M</au><au>Tran, Phu V</au><au>Georgieff, Michael K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neonatal mouse hippocampus: phlebotomy-induced anemia diminishes and treatment with erythropoietin partially rescues mammalian target of rapamycin signaling</atitle><jtitle>Pediatric research</jtitle><stitle>Pediatr Res</stitle><addtitle>Pediatr Res</addtitle><date>2017-09-01</date><risdate>2017</risdate><volume>82</volume><issue>3</issue><spage>501</spage><epage>508</epage><pages>501-508</pages><issn>0031-3998</issn><eissn>1530-0447</eissn><abstract>Background
Phlebotomy-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.
Methods
Mice 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.
Results
PIA 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.
Conclusion
PIA compromises and rHuEpo treatment partially rescues a pathway regulating neuronal DNA transcription, protein translation, and structural complexity.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>28399115</pmid><doi>10.1038/pr.2017.88</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 631/61/51/2314 631/80/83/2359 692/699/1541/13 692/700/1720/3186 Anemia Iron Kinases Medicine Medicine & Public Health Neurology Pediatric Surgery Pediatrics Premature birth Proteins Rodents translational-investigation |
| title | Neonatal mouse hippocampus: phlebotomy-induced anemia diminishes and treatment with erythropoietin partially rescues mammalian target of rapamycin signaling |
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