The cognitive defects of neonatally irradiated mice are accompanied by changed synaptic plasticity, adult neurogenesis and neuroinflammation

TitleThe cognitive defects of neonatally irradiated mice are accompanied by changed synaptic plasticity, adult neurogenesis and neuroinflammation
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2014
AuthorsKempf, S.J., Casciati Arianna, Buratovic S., Janik D., von Toerne C., Ueffing M., Neff F., Moertl S., Stenerlöw B., Saran Anna, Atkinson M.J., Eriksson P., Pazzaglia Simonetta, and Tapio S.
JournalMolecular neurodegeneration
Volume9
Pagination57
ISSN17501326
Keywordsanimal, animal behavior, Animals, Behavior, Brain, cognition, Experimental, experimental radiation injury, Fluorescent Antibody Technique, Immunoblotting, immunohistochemistry, male, Mice, mouse, nerve cell plasticity, nervous system development, Neurogenesis, Neuronal Plasticity, newborn, Radiation Injuries, radiation response, signal transduction
Abstract

CONCLUSION: These data suggest that neurocognitive disorders may be induced in adults when exposed at a young age to low and moderate cranial doses of radiation. This raises concerns about radiation safety standards and regulatory practices. RESULTS: Significant alterations in spontaneous behaviour were observed at 2 and 4 months following a single 0.5 or 1.0 Gy exposure. Alterations in the brain proteome, transcriptome, and several miRNAs were analysed 6-7 months post-irradiation in the hippocampus, dentate gyrus (DG) and cortex. Signalling pathways related to synaptic actin remodelling such as the Rac1-Cofilin pathway were altered in the cortex and hippocampus. Further, synaptic proteins MAP-2 and PSD-95 were increased in the DG and hippocampus (1.0 Gy). The expression of synaptic plasticity genes Arc, c-Fos and CREB was persistently reduced at 1.0 Gy in the hippocampus and cortex. These changes were coupled to epigenetic modulation via increased levels of microRNAs (miR-132/miR-212, miR-134). Astrogliosis, activation of insulin-growth factor/insulin signalling and increased level of microglial cytokine TNFα indicated radiation-induced neuroinflammation. In addition, adult neurogenesis within the DG was persistently negatively affected after irradiation, particularly at 1.0 Gy. BACKGROUND/PURPOSE OF THE STUDY: Epidemiological evidence suggests that low doses of ionising radiation (≤1.0 Gy) produce persistent alterations in cognition if the exposure occurs at a young age. The mechanisms underlying such alterations are unknown. We investigated the long-term effects of low doses of total body gamma radiation on neonatally exposed NMRI mice on the molecular and cellular level to elucidate neurodegeneration.

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84965092792&doi=10.1186%2f1750-1326-9-57&partnerID=40&md5=6c32c5c1bd2d31a075b175bd4f3e5952
DOI10.1186/1750-1326-9-57