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长期、性别特异性的 GCRsim 和伽马辐射对携带阿尔茨海默病突变的老鼠大脑、心脏和肾脏的影响。

Long-Term, Sex-Specific Effects of GCRsim and Gamma Irradiation on the Brains, Hearts, and Kidneys of Mice with Alzheimer's Disease Mutations.

机构信息

Department of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.

Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.

出版信息

Int J Mol Sci. 2024 Aug 16;25(16):8948. doi: 10.3390/ijms25168948.

DOI:10.3390/ijms25168948
PMID:39201636
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11355020/
Abstract

Understanding the hazards of space radiation is imperative as astronauts begin voyaging on missions with increasing distances from Earth's protective shield. Previous studies investigating the acute or long-term effects of specific ions comprising space radiation have revealed threats to organs generally considered radioresistant, like the brain, and have shown males to be more vulnerable than their female counterparts. However, astronauts will be exposed to a combination of ions that may result in additive effects differing from those of any one particle species. To better understand this nuance, we irradiated 4-month-old male and female, wild-type and Alzheimer's-like mice with 0, 0.5, or 0.75 Gy galactic cosmic ray simulation (GCRsim) or 0, 0.75, or 2 Gy gamma radiation (wild-type only). At 11 months, mice underwent brain and heart MRIs or behavioral tests, after which they were euthanized to assess amyloid-beta pathology, heart and kidney gene expression and fibrosis, and plasma cytokines. Although there were no changes in amyloid-beta pathology, we observed many differences in brain MRIs and behavior, including opposite effects of GCRsim on motor coordination in male and female transgenic mice. Additionally, several genes demonstrated persistent changes in the heart and kidney. Overall, we found sex- and genotype-specific, long-term effects of GCRsim and gamma radiation on the brain, heart, and kidney.

摘要

了解空间辐射的危害至关重要,因为宇航员开始执行越来越远离地球保护屏障的任务。以前的研究调查了构成空间辐射的特定离子的急性或长期影响,这些研究揭示了对通常被认为具有抗辐射能力的器官的威胁,如大脑,并表明男性比女性更容易受到影响。然而,宇航员将暴露在可能导致与任何一种单一粒子种类的影响不同的加性效应的离子组合中。为了更好地理解这一细微差别,我们用 0、0.5 或 0.75 Gy 银河宇宙射线模拟(GCRsim)或 0、0.75 或 2 Gy 伽马射线(仅野生型)对 4 个月大的雄性和雌性、野生型和阿尔茨海默病样小鼠进行辐照。在 11 个月大时,小鼠接受大脑和心脏 MRI 或行为测试,然后进行安乐死以评估淀粉样蛋白-β病理学、心脏和肾脏基因表达和纤维化以及血浆细胞因子。尽管淀粉样蛋白-β病理学没有变化,但我们观察到大脑 MRI 和行为有许多差异,包括 GCRsim 对雄性和雌性转基因小鼠运动协调的相反影响。此外,一些基因在心脏和肾脏中表现出持久的变化。总的来说,我们发现 GCRsim 和伽马辐射对大脑、心脏和肾脏有性别和基因型特异性的长期影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8324/11355020/8fc71a5c88ab/ijms-25-08948-g008.jpg
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