Galactic cosmic radiation leads to cognitive impairment and increased aβ plaque accumulation in a mouse model of Alzheimer's disease.
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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23300905/?tool=EBI |
| _version_ | 1818458851993714688 |
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| author | Jonathan D Cherry Bin Liu Jeffrey L Frost Cynthia A Lemere Jacqueline P Williams John A Olschowka M Kerry O'Banion |
| author_facet | Jonathan D Cherry Bin Liu Jeffrey L Frost Cynthia A Lemere Jacqueline P Williams John A Olschowka M Kerry O'Banion |
| author_sort | Jonathan D Cherry |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T23:05:02Z |
| format | Article |
| id | doaj.art-5530699b5a6e4d6088669bcd501edaf5 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T23:05:02Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-5530699b5a6e4d6088669bcd501edaf52022-12-21T22:44:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5327510.1371/journal.pone.0053275Galactic cosmic radiation leads to cognitive impairment and increased aβ plaque accumulation in a mouse model of Alzheimer's disease.Jonathan D CherryBin LiuJeffrey L FrostCynthia A LemereJacqueline P WilliamsJohn A OlschowkaM Kerry O'BanionGalactic 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23300905/?tool=EBI |
| spellingShingle | Jonathan D Cherry Bin Liu Jeffrey L Frost Cynthia A Lemere Jacqueline P Williams John A Olschowka M Kerry O'Banion Galactic cosmic radiation leads to cognitive impairment and increased aβ plaque accumulation in a mouse model of Alzheimer's disease. PLoS ONE |
| title | Galactic cosmic radiation leads to cognitive impairment and increased aβ plaque accumulation in a mouse model of Alzheimer's disease. |
| title_full | Galactic cosmic radiation leads to cognitive impairment and increased aβ plaque accumulation in a mouse model of Alzheimer's disease. |
| title_fullStr | Galactic cosmic radiation leads to cognitive impairment and increased aβ plaque accumulation in a mouse model of Alzheimer's disease. |
| title_full_unstemmed | Galactic cosmic radiation leads to cognitive impairment and increased aβ plaque accumulation in a mouse model of Alzheimer's disease. |
| title_short | Galactic cosmic radiation leads to cognitive impairment and increased aβ plaque accumulation in a mouse model of Alzheimer's disease. |
| title_sort | galactic cosmic radiation leads to cognitive impairment and increased aβ plaque accumulation in a mouse model of alzheimer s disease |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23300905/?tool=EBI |
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