title: Neonatal exposure to a moderate dose of ionizing radiation causes behavioural defects and altered levels of tau protein in mice.
abstract: Medical use of ionizing radiation (IR) has great benefits for treatment and diagnostic imaging, but procedures as computerized tomography (CT) may deliver a significant radiation dose to the patient. Recently, awareness has been raised about possible non-cancer consequences from low dose exposure to IR during critical phases of perinatal and/or neonatal brain development. In the present study neonatal NMRI mice were whole body irradiated with a single dose of gamma radiation (0; 350 and 500 mGy) on postnatal day 10 (PND 10). At 2 and 4 months of age, mice of both sexes were observed for spontaneous behaviour in a novel home environment. The neuroproteins CaMKII, GAP-43, synaptophysin and total tau in male mouse cerebral cortex and hippocampus were analysed 24h post-irradiation and in adults at 6 months of age exposed to 0 or 500 mGy on PND 10. A significantly dose-response related deranged spontaneous behaviour in 2- and 4-month-old mice was observed, where both males and females displayed a modified habituation, indicating reduced cognitive function. The dose of 350 mGy seems to be a tentative threshold. Six-month-old male mice showed a significantly increased level of total tau in cerebral cortex after irradiation to 500 mGy compared to controls. This demonstrates that a single moderate dose of IR, given during a defined critical period of brain development, is sufficient to cause persistently reduced cognitive function. Moreover, an elevation of tau protein was observed in male mice displaying reduced cognitive function.
authors.affiliation: Department of Environmental Toxicology, Uppsala University, Norbyvägen 18A, SE-75236 Uppsala, Sweden. Electronic address: sonja.buratovic@ebc.uu.se.
authors.forename: Sonja
authors.initials: S
authors.lastname: Buratovic
authors.affiliation: Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Stenerlöw
authors.affiliation: Department of Environmental Toxicology, Uppsala University, Norbyvägen 18A, SE-75236 Uppsala, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Fredriksson
authors.affiliation: Department of Soil and Environment, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: Synnöve
authors.initials: S
authors.lastname: Sundell-Bergman
authors.affiliation: Department of Environmental Toxicology, Uppsala University, Norbyvägen 18A, SE-75236 Uppsala, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Viberg
authors.affiliation: Department of Environmental Toxicology, Uppsala University, Norbyvägen 18A, SE-75236 Uppsala, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Eriksson
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000528:radiation effects*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000032:analysis; D002540:Cerebral Cortex / Q000378:metabolism / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D019922:GAP-43 Protein / Q000032:analysis; D005720:Gamma Rays / Q000009:adverse effects*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000528:radiation effects; D016708:Synaptophysin / Q000032:analysis; D016875:tau Proteins / Q000032:analysis
chemical_list: D019922:GAP-43 Protein; D016708:Synaptophysin; C569015:Syp protein, mouse; D016875:tau Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: Behaviour; Brain development; Ionizing radiation; Neonatal; Tau