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Kempf, S.J. ; Sepe, S.* ; von Toerne, C. ; Janik, D. ; Neff, F. ; Hauck, S.M. ; Atkinson, M.J. ; Mastroberardino, P.G.* ; Tapio, S.

Neonatal irradiation leads to persistent proteome alterations involved in synaptic plasticity in the mouse hippocampus and cortex.

J. Proteome Res. 14, 4674-4686 (2015)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Recent epidemiological data indicate that radiation doses as low as those used in computer tomography may result in long-term neurocognitive side effects. The aim of this study was to elucidate long-term molecular alterations related to memory formation in the brain after low and moderate doses of gamma radiation. Female C57BL/6J mice were irradiated on postnatal day 10 with total body doses of 0.1 Gy, 0.5 Gy or 2.0 Gy; the control group was sham-irradiated. The proteome analysis of hippocampus, cortex and synaptosomes isolated from these brain regions indicated changes in ephrin-related, RhoGDI and axonal guidance signalling.. Immunoblotting and miRNA-quantification demonstrated an imbalance in the synapse morphology-related Rac1-Cofilin pathway and long-term potentiation-related CREB signalling. Proteome profiling also showed impaired oxidative phosphorylation, especially in the synaptic mitochondria. This was accompanied by an early (4 weeks) reduction of mitochondrial respiration capacity in the hippocampus. Although the respiratory capacity was restored by 24 weeks, the number of deregulated mitochondrial complex proteins was increased at this time. All observed changes were significant at doses of 0.5 Gy and 2.0 Gy but not at 0.1 Gy. This study strongly suggests that ionising radiation at the neonatal state triggers persistent proteomic alterations associated with synaptic impairment.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Brain ; Cerebellum ; Dendritic Spine ; Ionizing Radiation ; Memory ; Mir-132 ; Mitochondria ; Proteomics ; Rac1 ; Synapse
ISSN (print) / ISBN 1535-3893
e-ISSN 1535-3907
Zeitschrift Journal of Proteome Research
Quellenangaben Band: 14, Heft: 11, Seiten: 4674-4686 Artikelnummer: , Supplement: ,
Verlag American Chemical Society (ACS)
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Radiation Biology (ISB)
Institute of Pathology (PATH)
CF Metabolomics & Proteomics (CF-MPC)