Oxygen causes cell death in the developing brain
Substantial neurologic morbidity occurs in survivors of premature birth. Premature infants are exposed to partial oxygen pressures that are fourfold higher compared to intrauterine conditions, even if no supplemental oxygen is administered. Here we report that short exposures to nonphysiologic oxyge...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2004-11-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S096999610400172X |
| _version_ | 1818647920525705216 |
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| author | Ursula Felderhoff-Mueser Petra Bittigau Marco Sifringer Bozena Jarosz Elzbieta Korobowicz Lieselotte Mahler Turid Piening Axel Moysich Tilman Grune Friederike Thor Rolf Heumann Christoph Bührer Chrysanthy Ikonomidou |
| author_facet | Ursula Felderhoff-Mueser Petra Bittigau Marco Sifringer Bozena Jarosz Elzbieta Korobowicz Lieselotte Mahler Turid Piening Axel Moysich Tilman Grune Friederike Thor Rolf Heumann Christoph Bührer Chrysanthy Ikonomidou |
| author_sort | Ursula Felderhoff-Mueser |
| collection | DOAJ |
| description | Substantial neurologic morbidity occurs in survivors of premature birth. Premature infants are exposed to partial oxygen pressures that are fourfold higher compared to intrauterine conditions, even if no supplemental oxygen is administered. Here we report that short exposures to nonphysiologic oxygen levels can trigger apoptotic neurodegeneration in the brains of infant rodents. Vulnerability to oxygen neurotoxicity is confined to the first 2 weeks of life, a period characterized by rapid growth, which in humans expands from the sixth month of pregnancy to the third year of life.Oxygen caused oxidative stress, decreased expression of neurotrophins, and inactivation of survival signaling proteins Ras, extracellular signal-regulated kinase (ERK 1/2), and protein kinase B (Akt). The synRas-transgenic mice overexpressing constitutively activated Ras and phosphorylated kinases ERK1/2 in the brain were protected against oxygen neurotoxicity. Our findings reveal a mechanism that could potentially damage the developing brain of human premature neonates. |
| first_indexed | 2024-12-17T01:10:12Z |
| format | Article |
| id | doaj.art-d885d9a2f0154222b5fd3ee569655b60 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-17T01:10:12Z |
| publishDate | 2004-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-d885d9a2f0154222b5fd3ee569655b602022-12-21T22:09:09ZengElsevierNeurobiology of Disease1095-953X2004-11-01172273282Oxygen causes cell death in the developing brainUrsula Felderhoff-Mueser0Petra Bittigau1Marco Sifringer2Bozena Jarosz3Elzbieta Korobowicz4Lieselotte Mahler5Turid Piening6Axel Moysich7Tilman Grune8Friederike Thor9Rolf Heumann10Christoph Bührer11Chrysanthy Ikonomidou12Department of Neonatology, Humboldt University Berlin, Charité, Campus Virchow Klinikum, 13353 Berlin, GermanyDepartment of Pediatric Neurology, Humboldt University Berlin, Charité, Campus Virchow Klinikum, 13353 Berlin, Germany; Neuroscience Research Center, Humboldt University Berlin, Charité, 10117 Berlin, GermanyDepartment of Pediatric Neurology, Humboldt University Berlin, Charité, Campus Virchow Klinikum, 13353 Berlin, Germany; Neuroscience Research Center, Humboldt University Berlin, Charité, 10117 Berlin, GermanyDepartment of Clinical Pathology, Medical University of Lublin, PolandDepartment of Clinical Pathology, Medical University of Lublin, PolandDepartment of Neonatology, Humboldt University Berlin, Charité, Campus Virchow Klinikum, 13353 Berlin, GermanyDepartment of Neonatology, Humboldt University Berlin, Charité, Campus Virchow Klinikum, 13353 Berlin, GermanyDepartment of Neonatology, Humboldt University Berlin, Charité, Campus Virchow Klinikum, 13353 Berlin, GermanyNeuroscience Research Center, Humboldt University Berlin, Charité, 10117 Berlin, GermanyMolecular Neurobiochemistry, Ruhr University, Bochum, GermanyMolecular Neurobiochemistry, Ruhr University, Bochum, GermanyDepartment of Neonatology, Humboldt University Berlin, Charité, Campus Virchow Klinikum, 13353 Berlin, GermanyDepartment of Pediatric Neurology, Humboldt University Berlin, Charité, Campus Virchow Klinikum, 13353 Berlin, Germany; Neuroscience Research Center, Humboldt University Berlin, Charité, 10117 Berlin, Germany; Corresponding author. Department of Pediatric Neurology, Humboldt University Berlin, Charité, Children's Hospital, Campus Virchow, Augustenburger Platz 1, D-13353 Berlin, Germany. Fax: +49 30 450566920.Substantial neurologic morbidity occurs in survivors of premature birth. Premature infants are exposed to partial oxygen pressures that are fourfold higher compared to intrauterine conditions, even if no supplemental oxygen is administered. Here we report that short exposures to nonphysiologic oxygen levels can trigger apoptotic neurodegeneration in the brains of infant rodents. Vulnerability to oxygen neurotoxicity is confined to the first 2 weeks of life, a period characterized by rapid growth, which in humans expands from the sixth month of pregnancy to the third year of life.Oxygen caused oxidative stress, decreased expression of neurotrophins, and inactivation of survival signaling proteins Ras, extracellular signal-regulated kinase (ERK 1/2), and protein kinase B (Akt). The synRas-transgenic mice overexpressing constitutively activated Ras and phosphorylated kinases ERK1/2 in the brain were protected against oxygen neurotoxicity. Our findings reveal a mechanism that could potentially damage the developing brain of human premature neonates.http://www.sciencedirect.com/science/article/pii/S096999610400172XApoptosisDevelopmentInfant ratOxidative stressSurvivalOxygen |
| spellingShingle | Ursula Felderhoff-Mueser Petra Bittigau Marco Sifringer Bozena Jarosz Elzbieta Korobowicz Lieselotte Mahler Turid Piening Axel Moysich Tilman Grune Friederike Thor Rolf Heumann Christoph Bührer Chrysanthy Ikonomidou Oxygen causes cell death in the developing brain Neurobiology of Disease Apoptosis Development Infant rat Oxidative stress Survival Oxygen |
| title | Oxygen causes cell death in the developing brain |
| title_full | Oxygen causes cell death in the developing brain |
| title_fullStr | Oxygen causes cell death in the developing brain |
| title_full_unstemmed | Oxygen causes cell death in the developing brain |
| title_short | Oxygen causes cell death in the developing brain |
| title_sort | oxygen causes cell death in the developing brain |
| topic | Apoptosis Development Infant rat Oxidative stress Survival Oxygen |
| url | http://www.sciencedirect.com/science/article/pii/S096999610400172X |
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