Space-like 56Fe irradiation manifests mild, early sex-specific behavioral and neuropathological changes in wildtype and Alzheimer’s-like transgenic mice
| Autor: | Lee A. Trojanczyk, M. Kerry O'Banion, Qiaoqiao Shi, Paul A. Jones, Shuyan Wang, Bin Liu, Marcelo F. Di Carli, Robert G. Hinshaw, Paul Lorello, Jacqueline P. Williams, Jeffrey L. Frost, Vladimir Reiser, Kevin X. Le, Mi-Ae Park, William Trigg, Anthony P. Belanger, Cynthia A. Lemere, Shipra Dubey, Barbara J. Caldarone, Peter Holton |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine lcsh:Medicine Behavioural methods 0302 clinical medicine lcsh:Science Iron Radioisotopes Multidisciplinary Behavior Animal Microglia biology Brain Alzheimer's disease Experimental models of disease medicine.anatomical_structure Cerebral blood flow Female Genetically modified mouse medicine.medical_specialty Transgene Mice Transgenic Neuropathology Motor Activity Article 03 medical and health sciences Sex Factors Alzheimer Disease Internal medicine Presenilin-1 medicine Translocator protein Animals Humans Learning Neuroinflammation Inflammation Amyloid beta-Peptides business.industry lcsh:R Wild type Dose-Response Relationship Radiation Space Flight Astrobiology Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology biology.protein lcsh:Q business 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-17 (2019) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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