Space radiation is comprised of highly charged ions (HZE particles) and protons that are able to pass through matter and cause radiation-induced injury, including neuronal damage and degeneration, glial activation, and oxidative stress. Previous work demonstrated a worsening of Alzheimer's disease pathology in the APP/PS1 transgenic mouse model, however effects of space radiation on tau pathology have not been studied. To determine whether tau pathology is altered by HZE particle or proton irradiation, we exposed 3xTg mice, which acquire both amyloid plaque and tau pathology with age, to iron, silicon, or solar particle event (SPE) irradiation at 9 months of age and evaluated behavior and brain pathology at 16 months of age. We found no differences in performance in fear conditioning and novel object recognition tasks between groups of mice exposed to sham, iron (10 and 100 cGy), silicon (10 and 100 cGy), or solar particle event radiation (200 cGy), though female mice had higher freezing responses than males. 200 cGy SPE irradiated female mice had fewer plaques than sham-irradiated females but had no differences in tau pathology. Overall, females had worse amyloid and tau pathology at 16 months of age and demonstrated a reduced neuroinflammatory gene expression response to radiation. These findings uncover differences between mouse models following radiation injury and corroborate prior reports of sex differences within the 3xTg mouse model.

空间辐射由高电荷离子（HZE 粒子）和质子组成，它们能够穿过物质并导致辐射引起的损伤，包括神经元损伤和退化、神经胶质激活和氧化应激。先前的工作表明，APP/PS1 转基因小鼠模型中阿尔茨海默病的病理学恶化，但尚未研究空间辐射对 tau 病理学的影响。为了确定 tau 病理是否被 HZE 粒子或质子照射改变，我们将 3xTg 小鼠暴露于铁、硅或太阳粒子事件 (SPE) 照射，并在 9 个月大时进行了评估16 个月大时的行为和脑病理。我们发现暴露于假手术、铁（10 和 100 cGy）、硅（10 和 100 cGy）或太阳粒子事件辐射（200 cGy）的小鼠组在恐惧条件反射和新物体识别任务方面的表现没有差异，尽管雌性小鼠比雄性有更高的冷冻反应。200 cGy SPE 照射的雌性小鼠的斑块比假照射的雌性小鼠少，但 tau 病理学没有差异。总体而言，女性在 16 个月大时淀粉样蛋白和 tau 蛋白的病理状况更糟，并且表现出对辐射的神经炎症基因表达反应降低。这些发现揭示了辐射损伤后小鼠模型之间的差异，并证实了先前关于 3xTg 小鼠模型中性别差异的报告。尽管雌性老鼠比雄性老鼠有更高的冰冻反应。200 cGy SPE 照射的雌性小鼠的斑块比假照射的雌性小鼠少，但 tau 病理学没有差异。总体而言，女性在 16 个月大时淀粉样蛋白和 tau 蛋白的病理状况更糟，并且表现出对辐射的神经炎症基因表达反应降低。这些发现揭示了辐射损伤后小鼠模型之间的差异，并证实了先前关于 3xTg 小鼠模型中性别差异的报告。尽管雌性老鼠比雄性老鼠有更高的冰冻反应。200 cGy SPE 照射的雌性小鼠的斑块比假照射的雌性小鼠少，但 tau 病理学没有差异。总体而言，女性在 16 个月大时淀粉样蛋白和 tau 蛋白的病理状况更糟，并且表现出对辐射的神经炎症基因表达反应降低。这些发现揭示了辐射损伤后小鼠模型之间的差异，并证实了先前关于 3xTg 小鼠模型中性别差异的报告。