title: Galactic cosmic radiation leads to cognitive impairment and increased aβ plaque accumulation in a mouse model of Alzheimer's disease.
abstract: Galactic Cosmic Radiation consisting of high-energy, high-charged (HZE) particles poses a significant threat to future astronauts in deep space. Aside from cancer, concerns have been raised about late degenerative risks, including effects on the brain. In this study we examined the effects of (56)Fe particle irradiation in an APP/PS1 mouse model of Alzheimer's disease (AD). We demonstrated 6 months after exposure to 10 and 100 cGy (56)Fe radiation at 1 GeV/µ, that APP/PS1 mice show decreased cognitive abilities measured by contextual fear conditioning and novel object recognition tests. Furthermore, in male mice we saw acceleration of Aβ plaque pathology using Congo red and 6E10 staining, which was further confirmed by ELISA measures of Aβ isoforms. Increases were not due to higher levels of amyloid precursor protein (APP) or increased cleavage as measured by levels of the β C-terminal fragment of APP. Additionally, we saw no change in microglial activation levels judging by CD68 and Iba-1 immunoreactivities in and around Aβ plaques or insulin degrading enzyme, which has been shown to degrade Aβ. However, immunohistochemical analysis of ICAM-1 showed evidence of endothelial activation after 100 cGy irradiation in male mice, suggesting possible alterations in Aβ trafficking through the blood brain barrier as a possible cause of plaque increase. Overall, our results show for the first time that HZE particle radiation can increase Aβ plaque pathology in an APP/PS1 mouse model of AD.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, United States of America.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Cherry
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Frost
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Lemere
authors.forename: Jacqueline P
authors.initials: JP
authors.lastname: Williams
authors.forename: John A
authors.initials: JA
authors.lastname: Olschowka
authors.forename: M Kerry
authors.initials: MK
authors.lastname: O'Banion
mesh_terms: D000544:Alzheimer Disease / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D003072:Cognition Disorders / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D003359:Cosmic Radiation / Q000009:adverse effects*; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D058225:Plaque, Amyloid / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1 / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1