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 Ercc2 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.

中文翻译：

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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

摘要

目的

在医学中越来越多地使用低剂量电离辐射需要对其对大脑、行为的长期影响及其与神经退行性疾病易感性的可能关联进行系统研究。因此，我们分析了 10 周龄单次低剂量照射与中等和较高剂量相比对小鼠运动、情绪相关和感觉运动行为以及海马神经胶质细胞群的长期影响。

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（注射后 4、12和 18 个月）、性别和基因型（野生型与具有Ercc2 DNA 修复基因点突变的小鼠）对行为的影响.

结果

高剂量 (0.5 Gy) 在注射后 4 个月对感觉运动恢复有早发性不良影响，在注射后 12 个月和 18 个月对运动产生迟发性负作用。起效（18 个月）对感觉运动募集和探索行为的保护作用。24 个月后齿状回小胶质细胞和星形胶质细胞的定量和形态学表征表明，高剂量照射（0.125 和 0.5 Gy）后免疫活性增强，而相反，低剂量（0.063 Gy）诱导更多的神经保护功能。

结论

这是首批证明在成年期单次辐射事件后对大脑和行为产生这种长期和迟发性影响的研究之一。