Galactic cosmic radiation leads to cognitive impairment and increased aβ plaque accumulation in a mouse model of Alzheimer's disease.
Galactic cosmic radiation leads to cognitive impairment and increased aβ plaque accumulation in a mouse model of Alzheimer's disease.
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DOI：
10.1371/journal.pone.0053275
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
O'Banion MK
中科院分区：
文献类型：
--
作者：
Cherry JD;Liu B;Frost JL;Lemere CA;Williams JP;Olschowka JA;O'Banion MK
银河宇宙辐射由高能、高电荷（HZE）粒子组成，对未来深空宇航员构成重大威胁。除了癌症，人们还对晚期退行性风险，包括对大脑的影响表示担忧。在本研究中，我们研究了56Fe粒子辐照对APP/PS1老年痴呆症（AD）小鼠模型的影响。我们证明，在暴露于10和100 cGy的1 GeV/µ56Fe辐射6个月后，APP/PS1小鼠在情境恐惧条件反射和新物体识别测试中表现出认知能力下降。此外，在雄性小鼠中，我们通过刚果红和6E10染色观察到Aβ斑块病理加速，这进一步通过ELISA检测Aβ同工型得到证实。增加不是由于淀粉样蛋白前体蛋白（APP）水平升高或APP β c末端片段水平测定的劈裂增加。此外，我们通过β斑块内和周围的CD68和Iba-1免疫反应性或胰岛素降解酶（已被证明可以降解Aβ）来判断小胶质细胞激活水平没有变化。然而，ICAM-1的免疫组织化学分析显示，雄性小鼠在100 cGy照射后内皮细胞活化，这表明a β通过血脑屏障运输的改变可能是斑块增加的可能原因。总之，我们的研究结果首次表明，HZE粒子辐射可以增加APP/PS1 AD小鼠模型中的Aβ斑块病理。
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 56Fe particle irradiation in an APP/PS1 mouse model of Alzheimer’s disease (AD). We demonstrated 6 months after exposure to 10 and 100 cGy 56Fe 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.
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影响因子：
6.2
作者：
Matousek, Sarah B.;Ghosh, Simantini;Shaftel, Solomon S.;Kyrkanides, Stephanos;Olschowka, John A.;O'Banion, M. Kerry
通讯作者：
O'Banion, M. Kerry
影响因子：
15.1
作者：
Chakrabarty P;Herring A;Ceballos-Diaz C;Das P;Golde TE
通讯作者：
Golde TE
影响因子：
14
作者：
通讯作者：
--
影响因子：
9.3
作者：
Krstic D;Madhusudan A;Doehner J;Vogel P;Notter T;Imhof C;Manalastas A;Hilfiker M;Pfister S;Schwerdel C;Riether C;Meyer U;Knuesel I
通讯作者：
Knuesel I
影响因子：
9.3
作者：
Erickson MA;Hartvigson PE;Morofuji Y;Owen JB;Butterfield DA;Banks WA
通讯作者：
Banks WA