Neonatal exposure to a single low dose of ionising radiation causes persistent disruptions in cognitive abilities and increased levels of tau in mice

• Ionising radiation (IR) is extensively used in the medical field for treatment and diagnostics. Concern has been raised about possible negative consequences from low dose exposure to IR during critical phases of perinatal and/or neonatal brain development. The brain growth spurt, which is characterized by maturation of axonal and dendritic outgrowth, establishment of neural connections and acquisition of new motor and sensory abilities, occurs perinatally in humans and neonatally in mice. By using the neonatal mouse as an animal model we are able to study the effect of IR during early periods of brain development and which consequences it has for the adult animal.Neonatal NMRI mice were irradiated (0; 0.35 and 0.5 Gy) at one single occasion on postnatal day 10. At 2- and 4-months of age, spontaneous behaviour was tested in a novel home environment and parameters observed were locomotion, rearing and total activity. Analyses of important neuroproteins in cerebral cortex were performed 24h following irradiation (0 and 0.5 Gy) and at 6-months of age.Observations of spontaneous behaviour revealed a significantly deranged behaviour in 2- and 4-month old mice of both sexes irradiated with 0.35 or 0.5 Gy in a dose response related manner. The observed reduced activity during the beginning of the test period and increased activity at the end of the test period indicates a lack of habituation capacity and disrupted cognitive functions. Neuroprotein analyses of cerebral cortex 24h after irradiation and at 6-months of age showed a significantly increased level of tau in mice irradiated with 0.5 Gy compared to controls. This demonstrates that a single dose of IR, given at a defined critical period during brain development, is sufficient to cause persistently reduced cognitive functions and increased levels of tau in mice. 

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