Ion mobility-enhanced MSE-based Label-free Analysis Reveals Effects of Low-dose Radiation Post Contextual Fear Conditioning Training on the Mouse Hippocampal Proteome

摘要

Recent advances in the field of biodosimetry have shown that the response of biological systems to ionizing radiation is complex and depends on the type and dose of radiation, the tissue(s) exposed, and the time lapsed after exposure. The biological effects of low dose radiation on learning and memory are not well understood. An ion mobility-enhanced data-independent acquisition (MS^E) approach in conjunction with the IsoQuant software tool was utilized for label-free quantification of hippocampal proteins with the goal of determining protein alteration associated with low-dose whole body ionizing radiation (X-rays, 1 Gy) of 5.5-month-old male C57BL/6J mice post contextual fear conditioning training. Global proteome analysis revealed deregulation of 73 proteins (out 399 proteins). Deregulated proteins indicated adverse effects of irradiation on myelination and perturbation of energy metabolism pathways involving a shift from the TCA cycle to glutamate oxidation. Our findings also indicate that proteins associated with synaptic activity, including vesicle recycling and neurotransmission, were altered in the irradiated mice. The elevated LTP and decreased LTD suggest improved synaptic transmission and enhanced efficiency of neurotransmitter release which would be consistent with the observed comparable contextual fear memory performance of the mice following post-training whole body or sham-irradiation.