Space-like 56Fe irradiation manifests mild, early sex-specific behavioral and neuropathological changes in wildtype and Alzheimer's-like transgenic mice

太空类 56Fe 辐射在野生型和阿尔茨海默氏症样转基因小鼠中表现出轻微的早期性别特异性行为和神经病理学变化

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作者:Bin Liu, Robert G Hinshaw, Kevin X Le, Mi-Ae Park, Shuyan Wang, Anthony P Belanger, Shipra Dubey, Jeffrey L Frost, Qiaoqiao Shi, Peter Holton, Lee Trojanczyk, Vladimir Reiser, Paul A Jones, William Trigg, Marcelo F Di Carli, Paul Lorello, Barbara J Caldarone, Jacqueline P Williams, M Kerry O'Banion,

Abstract

Space travel will expose people to high-energy, heavy particle radiation, and the cognitive deficits induced by this exposure are not well understood. To investigate the short-term effects of space radiation, we irradiated 4-month-old Alzheimer's disease (AD)-like transgenic (Tg) mice and wildtype (WT) littermates with a single, whole-body dose of 10 or 50 cGy 56Fe ions (1 GeV/u) at Brookhaven National Laboratory. At ~1.5 months post irradiation, behavioural testing showed sex-, genotype-, and dose-dependent changes in locomotor activity, contextual fear conditioning, grip strength, and motor learning, mainly in Tg but not WT mice. There was little change in general health, depression, or anxiety. Two months post irradiation, microPET imaging of the stable binding of a translocator protein ligand suggested no radiation-specific change in neuroinflammation, although initial uptake was reduced in female mice independently of cerebral blood flow. Biochemical and immunohistochemical analyses revealed that radiation reduced cerebral amyloid-β levels and microglia activation in female Tg mice, modestly increased microhemorrhages in 50 cGy irradiated male WT mice, and did not affect synaptic marker levels compared to sham controls. Taken together, we show specific short-term changes in neuropathology and behaviour induced by 56Fe irradiation, possibly having implications for long-term space travel.

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