1. ¹Department of Pediatric Neurology, Charité, University Medical School, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany
2. ²Institute of Human Genetics, Charité, University Medical School, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany
3. ³Department of Pediatric Neurology, University Children's Hospital, Technical University Dresden, Fetscher Str. 74, 01307 Dresden, Germany
4. ⁴Department of Neonatology, Charité, University Medical School, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany

Correspondence: AM Kaindl, Department of Pediatric Neurology, Charité, University Medical School, Augustenburger Platz 1, 13353 Berlin, Germany. Tel: +49 30 450 566112; Fax: +49 30 450 566920; E-mail: angela.kaindl@charite.de

Received 15 March 2005; Revised 31 August 2005; Accepted 22 September 2005; Published online 28 October 2005.

Abstract

The developing mammalian brain experiences a period of rapid growth during which various otherwise innocuous environmental factors cause widespread apoptotic neuronal death. To gain insight into developmental events influenced by a premature exposure to high oxygen levels and identify proteins engaged in neurodegenerative and reparative processes, we analyzed mouse brain proteome changes at P7, P14 and P35 caused by an exposure to hyperoxia at P6. Changes detected in the brain proteome suggested that hyperoxia leads to oxidative stress and apoptotic neuronal death. These changes were consistent with results of histological and biochemical evaluation of the brains, which revealed widespread apoptotic neuronal death and increased levels of protein carbonyls. Furthermore, we detected changes in proteins involved in synaptic function, cell proliferation and formation of neuronal connections, suggesting interference of oxidative stress with these developmental events. These effects are age-dependent, as they did not occur in mice subjected to hyperoxia in adolescence.