American Chemical Society, Journal of Proteome Research, 5(14), p. 2055-2064, 2015
DOI: 10.1021/acs.jproteome.5b00114
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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 signalling pathways. The aim of this study was to elucidate the molecular mechanisms behind learning and memory deficits after acute low and moderate doses of ionising radiation. Female C57BL/6J mice were irradiated on postnatal day 10 (PND10) with gamma doses of 0.1 Gy or 0.5 Gy. This was followed by evaluation of the cellular proteome, pathway-focussed transcriptome and neurological development/disease-focussed miRNAome of hippocampus and cortex 24 hours post-irradiation. Our analysis showed that signalling 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 observed predominately in the cortex at 0.1 Gy 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 signalling 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.