American Chemical Society, Journal of Proteome Research, 11(14), p. 4674-4686, 2015
DOI: 10.1021/acs.jproteome.5b00564
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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.