title: The cognitive defects of neonatally irradiated mice are accompanied by changed synaptic plasticity, adult neurogenesis and neuroinflammation.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Kempf
authors.forename: Arianna
authors.initials: A
authors.lastname: Casciati
authors.forename: Sonja
authors.initials: S
authors.lastname: Buratovic
authors.forename: Dirk
authors.initials: D
authors.lastname: Janik
authors.forename: Christine
authors.initials: C
authors.lastname: von Toerne
authors.forename: Marius
authors.initials: M
authors.lastname: Ueffing
authors.forename: Frauke
authors.initials: F
authors.lastname: Neff
authors.forename: Simone
authors.initials: S
authors.lastname: Moertl
authors.forename: Bo
authors.initials: B
authors.lastname: Stenerlöw
authors.forename: Anna
authors.initials: A
authors.lastname: Saran
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Atkinson
authors.forename: Per
authors.initials: P
authors.lastname: Eriksson
authors.forename: Simonetta
authors.initials: S
authors.lastname: Pazzaglia
authors.affiliation: Institute of Radiation Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany. soile.tapio@helmholtz-muenchen.de.
authors.forename: Soile
authors.initials: S
authors.lastname: Tapio
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000528:radiation effects; D001921:Brain / Q000528:radiation effects*; D003071:Cognition / Q000528:radiation effects*; D005455:Fluorescent Antibody Technique; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D055495:Neurogenesis / Q000528:radiation effects*; D009473:Neuronal Plasticity / Q000528:radiation effects*; D011833:Radiation Injuries, Experimental; D015398:Signal Transduction / Q000528:radiation effects