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Low-dose ionizing radiation rapidly affects mitochondrial and synaptic signaling pathways in murine hippocampus and cortex.
J. Proteome Res. 14, 2055-2064 (2015)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Creb ; Ltp ; Dendritic Spine ; Ionizing Radiation ; Learning ; Memory ; Microrna ; Proteomics ; Synaptic Plasticity; Adhesion Molecule Ncam; Alzheimers-disease; Adult Neurogenesis; Cognitive Deficits; Gene-transcription; Dendritic Spines; Protein-levels; Brain; Exposure; Mice
ISSN (print) / ISBN
1535-3893
e-ISSN
1535-3907
Journal
Journal of Proteome Research
Quellenangaben
Volume: 14,
Issue: 5,
Pages: 2055-2064
Publisher
American Chemical Society (ACS)
Publishing Place
Washington
Non-patent literature
Publications
Reviewing status
Peer reviewed