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单次辐射事件对行为和神经胶质细胞的剂量依赖性长期影响。

Dose-dependent long-term effects of a single radiation event on behaviour and glial cells.

机构信息

Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany.

Institute of Pathology, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Germany.

出版信息

Int J Radiat Biol. 2021;97(2):156-169. doi: 10.1080/09553002.2021.1857455. Epub 2020 Dec 15.

Abstract

PURPOSE

The increasing use of low-dose ionizing radiation in medicine requires a systematic study of its long-term effects on the brain, behaviour and its possible association with neurodegenerative disease vulnerability. Therefore, we analysed the long-term effects of a single low-dose irradiation exposure at 10 weeks of age compared to medium and higher doses on locomotor, emotion-related and sensorimotor behaviour in mice as well as on hippocampal glial cell populations.

MATERIALS AND METHODS

We determined the influence of radiation dose (0, 0.063, 0.125 or 0.5 Gy), time post-irradiation (4, 12 and 18 months p.i.), sex and genotype (wild type versus mice with DNA repair gene point mutation) on behaviour.

RESULTS

The high dose (0.5 Gy) had early-onset adverse effects at 4 months p.i. on sensorimotor recruitment and late-onset negative locomotor effects at 12 and 18 months p.i. Notably, the low dose (0.063 Gy) produced no early effects but subtle late-onset (18 months) protective effects on sensorimotor recruitment and exploratory behaviour. Quantification and morphological characterization of the microglial and the astrocytic cells of the dentate gyrus 24 months p.i. indicated heightened immune activity after high dose irradiation (0.125 and 0.5 Gy) while conversely, low dose (0.063 Gy) induced more neuroprotective features.

CONCLUSION

This is one of the first studies demonstrating such long-term and late-onset effects on brain and behaviour after a single radiation event in adulthood.

摘要

目的

医学中低剂量电离辐射的应用日益增多,因此需要系统研究其对大脑的长期影响、行为表现以及与神经退行性疾病易感性的可能关联。因此,我们分析了在 10 周龄时单次低剂量照射(与中剂量和高剂量相比)对小鼠的运动、情绪相关和感觉运动行为以及海马神经胶质细胞群体的长期影响。

材料和方法

我们确定了辐射剂量(0、0.063、0.125 或 0.5 Gy)、辐射后时间(4、12 和 18 个月)、性别和基因型(野生型与 DNA 修复基因突变型)对行为的影响。

结果

高剂量(0.5 Gy)在 4 个月时出现早期的感觉运动募集不良,在 12 和 18 个月时出现晚期的负性运动效应。值得注意的是,低剂量(0.063 Gy)没有早期效应,但在 18 个月时有轻微的晚期保护作用,对感觉运动募集和探索行为有保护作用。24 个月时,齿状回的小胶质细胞和星形胶质细胞的定量和形态学特征表明,高剂量(0.125 和 0.5 Gy)照射后免疫活性增强,而相反,低剂量(0.063 Gy)诱导出更多的神经保护特征。

结论

这是首次研究表明,在成年期单次辐射事件后,对大脑和行为会产生如此长期和晚期的影响。

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