Low-Dose Ionizing Radiation Rapidly Affects Mitochondrial and Synaptic Signaling Pathways in Murine Hippocampus and Cortex

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.