title: The biobehavioral and neuroimmune impact of low-dose ionizing radiation.
abstract: In the clinical setting, repeated exposures (10-30) to low-doses of ionizing radiation (≤200 cGy), as seen in radiotherapy for cancer, causes fatigue. Almost nothing is known, however, about the fatigue inducing effects of a single exposure to environmental low-dose ionizing radiation that might occur during high-altitude commercial air flight, a nuclear reactor accident or a solar particle event (SPE). To investigate the short-term impact of low-dose ionizing radiation on mouse biobehaviors and neuroimmunity, male CD-1 mice were whole body irradiated with 50 cGy or 200 cGy of gamma or proton radiation. Gamma radiation was found to reduce spontaneous locomotor activity by 35% and 36%, respectively, 6 h post irradiation. In contrast, the motivated behavior of social exploration was un-impacted by gamma radiation. Examination of pro-inflammatory cytokine gene transcripts in the brain demonstrated that gamma radiation increased hippocampal TNF-α expression as early as 4 h post-irradiation. This was coupled to subsequent increases in IL-1RA (8 and 12 h post irradiation) in the cortex and hippocampus and reductions in activity-regulated cytoskeleton-associated protein (Arc) (24 h post irradiation) in the cortex. Finally, restraint stress was a significant modulator of the neuroimmune response to radiation blocking the ability of 200 cGy gamma radiation from impairing locomotor activity and altering the brain-based inflammatory response to irradiation. Taken together, these findings indicate that low-dose ionizing radiation rapidly activates the neuroimmune system potentially causing early onset fatigue-like symptoms in mice.
authors.affiliation: Department of Animal Sciences, University of Illinois, Urbana, IL, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: York
authors.forename: Neil A
authors.initials: NA
authors.lastname: Blevins
authors.forename: Daryl D
authors.initials: DD
authors.lastname: Meling
authors.forename: Molly B
authors.initials: MB
authors.lastname: Peterlin
authors.forename: Daila S
authors.initials: DS
authors.lastname: Gridley
authors.forename: Keith A
authors.initials: KA
authors.lastname: Cengel
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Freund
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism / Q000528:radiation effects; D003598:Cytoskeletal Proteins; D004307:Dose-Response Relationship, Radiation; D005106:Exploratory Behavior / Q000528:radiation effects; D005221:Fatigue / Q000139:chemically induced; D005720:Gamma Rays; D006624:Hippocampus / Q000378:metabolism / Q000528:radiation effects; D053590:Interleukin 1 Receptor Antagonist Protein / Q000096:biosynthesis; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins; D015213:Neuroimmunomodulation / Q000528:radiation effects*; D011839:Radiation, Ionizing; D012149:Restraint, Physical / Q000523:psychology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014916:Whole-Body Irradiation
chemical_list: D003598:Cytoskeletal Proteins; D053590:Interleukin 1 Receptor Antagonist Protein; D009419:Nerve Tissue Proteins; D014409:Tumor Necrosis Factor-alpha; C092069:activity regulated cytoskeletal-associated protein