title: Low-dose ionizing radiation rapidly affects mitochondrial and synaptic signaling pathways in murine hippocampus and cortex.
abstract: The increased use of radiation-based medical imaging methods such as computer tomography is a matter of concern due to potential radiation-induced adverse effects. Efficient protection against such detrimental effects has not been possible due to inadequate understanding of radiation-induced alterations in signaling pathways. The aim of this study was to elucidate the molecular mechanisms behind learning and memory deficits after acute low and moderate doses of ionizing radiation. Female C57BL/6J mice were irradiated on postnatal day 10 (PND10) with gamma doses of 0.1 or 0.5 Gy. This was followed by evaluation of the cellular proteome, pathway-focused transcriptome, and neurological development/disease-focused miRNAome of hippocampus and cortex 24 h postirradiation. Our analysis showed that signaling pathways related to mitochondrial and synaptic functions were changed by acute irradiation. This may lead to reduced mitochondrial function paralleled by enhanced number of dendritic spines and neurite outgrowth due to elevated long-term potentiation, triggered by increased phosphorylated CREB. This was predominately observed in the cortex at 0.1 and 0.5 Gy and in the hippocampus only at 0.5 Gy. Moreover, a radiation-induced increase in the expression of several neural miRNAs associated with synaptic plasticity was found. The early changes in signaling pathways related to memory formation may be associated with the acute neurocognitive side effects in patients after brain radiotherapy but might also contribute to late radiation-induced cognitive injury.
authors: †Institute of Radiation Biology, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
authors: Stefan J
authors: SJ
authors: Kempf
authors: †Institute of Radiation Biology, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
authors: Simone
authors: S
authors: Moertl
authors: ‡Department of Genetics, Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors: Sara
authors: S
authors: Sepe
authors: §Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
authors: Christine
authors: C
authors: von Toerne
authors: §Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
authors: Stefanie M
authors: SM
authors: Hauck
authors: †Institute of Radiation Biology, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.|∥Chair of Radiation Biology, Technical University Munich, Arcisstrasse 21, 80333 Munich, Germany.
authors: Michael J
authors: MJ
authors: Atkinson
authors: ‡Department of Genetics, Erasmus Medical Center, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.
authors: Pier G
authors: PG
authors: Mastroberardino
authors: †Institute of Radiation Biology, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
authors: Soile
authors: S
authors: Tapio
mesh_terms: D000818:Animals; D050882:CREB-Binding Protein / Q000235:genetics / Q000378:metabolism; D002540:Cerebral Cortex / Q000502:physiology / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays; D015870:Gene Expression; D006624:Hippocampus / Q000502:physiology / Q000528:radiation effects*; D006801:Humans; D017774:Long-Term Potentiation / Q000528:radiation effects*; D008568:Memory / Q000528:radiation effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism / Q000528:radiation effects*; D010766:Phosphorylation; D020543:Proteome / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects; D013569:Synapses / Q000502:physiology / Q000528:radiation effects*; D059467:Transcriptome
chemical_list: D020543:Proteome; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse
keywords: CREB; LTP; dendritic spine; ionizing radiation; learning; memory; microRNA; proteomics; synaptic plasticity