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 @entity19 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 @entity5844 -Cofilin pathway were altered in the cortex and hippocampus. Further, synaptic proteins @entity7001 and @entity39061 were increased in the DG and hippocampus (1.0  Gy). The expression of synaptic plasticity genes Arc, @entity9830 and @entity15983 was persistently reduced at 1.0  Gy in the hippocampus and cortex. These changes were coupled to epigenetic modulation via increased levels of microRNAs ( @entity33708 / @entity53437 , @entity68727 ). Astrogliosis, activation of insulin-growth factor/insulin signalling and increased level of microglial cytokine @entity637 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 @entity149 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.

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

@entity33708 :: ('387150(Tax:10090)', 'Gene') :: ['miR-132'] @entity39061 :: ('13385(Tax:10090)', 'Gene') :: ['PSD-95'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity149 :: ('MESH:D002493', 'Disease') :: ['neurocognitive disorders'] @entity15983 :: ('12912(Tax:10090)', 'Gene') :: ['CREB'] @entity9830 :: ('14281(Tax:10090)', 'Gene') :: ['c-Fos'] @entity5844 :: ('19353(Tax:10090)', 'Gene') :: ['Rac1'] @entity7001 :: ('17756(Tax:10090)', 'Gene') :: ['MAP-2'] @entity68727 :: ('387152(Tax:10090)', 'Gene') :: ['miR-134'] @entity53437 :: ('387208(Tax:10090)', 'Gene') :: ['miR-212'] @entity637 :: ('21926(Tax:10090)', 'Gene') :: ['TNFa']
@entity19 :: (10090,Species) :: ['mice']
