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Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2014

Open Access 01-12-2014 | Research article

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

Authors: Stefan J Kempf, Arianna Casciati, Sonja Buratovic, Dirk Janik, Christine von Toerne, Marius Ueffing, Frauke Neff, Simone Moertl, Bo Stenerlöw, Anna Saran, Michael J Atkinson, Per Eriksson, Simonetta Pazzaglia, Soile Tapio

Published in: Molecular Neurodegeneration | Issue 1/2014

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Abstract

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.

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.

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.
Appendix
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Metadata
Title
The cognitive defects of neonatally irradiated mice are accompanied by changed synaptic plasticity, adult neurogenesis and neuroinflammation
Authors
Stefan J Kempf
Arianna Casciati
Sonja Buratovic
Dirk Janik
Christine von Toerne
Marius Ueffing
Frauke Neff
Simone Moertl
Bo Stenerlöw
Anna Saran
Michael J Atkinson
Per Eriksson
Simonetta Pazzaglia
Soile Tapio
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2014
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/1750-1326-9-57

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