Kempf Stefan J, Casciati Arianna, Buratovic Sonja, Janik Dirk, von Toerne Christine, Ueffing Marius, Neff Frauke, Moertl Simone, Stenerlöw Bo, Saran Anna, Atkinson Michael J, Eriksson Per, Pazzaglia Simonetta, Tapio Soile
Institute of Radiation Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany.
Mol Neurodegener. 2014 Dec 16;9:57. doi: 10.1186/1750-1326-9-57.
BACKGROUND/PURPOSE OF THE STUDY: Epidemiological evidence suggests that low doses of ionising radiation (≤1.0 Gy) produce persistent alterations in cognition if the exposure occurs at a young age. The mechanisms underlying such alterations are unknown. We investigated the long-term effects of low doses of total body gamma radiation on neonatally exposed NMRI mice on the molecular and cellular level to elucidate neurodegeneration.
Significant alterations in spontaneous behaviour were observed at 2 and 4 months following a single 0.5 or 1.0 Gy exposure. Alterations in the brain proteome, transcriptome, and several miRNAs were analysed 6-7 months post-irradiation in the hippocampus, dentate gyrus (DG) and cortex. Signalling pathways related to synaptic actin remodelling such as the Rac1-Cofilin pathway were altered in the cortex and hippocampus. Further, synaptic proteins MAP-2 and PSD-95 were increased in the DG and hippocampus (1.0 Gy). The expression of synaptic plasticity genes Arc, c-Fos and CREB was persistently reduced at 1.0 Gy in the hippocampus and cortex. These changes were coupled to epigenetic modulation via increased levels of microRNAs (miR-132/miR-212, miR-134). Astrogliosis, activation of insulin-growth factor/insulin signalling and increased level of microglial cytokine TNFα indicated radiation-induced neuroinflammation. In addition, adult neurogenesis within the DG was persistently negatively affected after irradiation, particularly at 1.0 Gy.
These data suggest that neurocognitive disorders may be induced in adults when exposed at a young age to low and moderate cranial doses of radiation. This raises concerns about radiation safety standards and regulatory practices.
研究背景/目的：流行病学证据表明，如果在幼年时暴露于低剂量电离辐射（≤1.0 Gy），会导致认知功能出现持续性改变。这种改变的潜在机制尚不清楚。我们在分子和细胞水平上研究了低剂量全身γ辐射对新生期暴露的NMRI小鼠的长期影响，以阐明神经退行性变。
单次暴露于0.5或1.0 Gy后，在2个月和4个月时观察到自发行为有显著改变。在照射后6 - 7个月，分析了海马体、齿状回（DG）和皮质中的脑蛋白质组、转录组以及几种微小RNA的变化。与突触肌动蛋白重塑相关的信号通路，如Rac1 - Cofilin通路，在皮质和海马体中发生了改变。此外，DG和海马体（1.0 Gy）中的突触蛋白MAP - 2和PSD - 95增加。海马体和皮质中，1.0 Gy剂量下突触可塑性基因Arc、c - Fos和CREB的表达持续降低。这些变化与微小RNA（miR - 132/miR - 212、miR - 134）水平升高导致的表观遗传调控有关。星形胶质细胞增生、胰岛素 - 生长因子/胰岛素信号激活以及小胶质细胞细胞因子TNFα水平升高表明存在辐射诱导的神经炎症。此外，照射后DG内的成年神经发生持续受到负面影响，尤其是在1.0 Gy剂量时。
这些数据表明，幼年时暴露于低至中等剂量的颅脑辐射可能会在成年后诱发神经认知障碍。这引发了对辐射安全标准和监管措施的关注。
