Oxygen causes cell death in the developing brain

Neurobiology of Disease

Marco Sifringer¹  Elzbieta Korobowicz¹  Turid Piening²  Lieselotte Mahler²  Friederike Thor³  Tilman Grune³  Ursula Felderhoff-Mueser³  Axel Moysich³  Petra Bittigau⁴  Bozena Jarosz⁴  Chrysanthy Ikonomidou⁵  Christoph Bührer⁵  Rolf Heumann⁶ 

[1] Neuroscience Research Center, Humboldt University Berlin, Charité, 10117 Berlin, Germany;Department of Clinical Pathology, Medical University of Lublin, Poland;Department of Neonatology, Humboldt University Berlin, Charité, Campus Virchow Klinikum, 13353 Berlin, Germany;Department of Pediatric Neurology, Humboldt University Berlin, Charité, Campus Virchow Klinikum, 13353 Berlin, Germany;Molecular Neurobiochemistry, Ruhr University, Bochum, Germany;Neuroscience Research Center, Humboldt University Berlin, Charité, 10117 Berlin, Germany;

关键词: Apoptosis;    Development;    Infant rat;    Oxidative stress;    Survival;    Oxygen;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown