The cognitive defects of neonatally irradiated mice are accompanied by changed synaptic plasticity, adult neurogenesis and neuroinflammation.
The cognitive defects of neonatally irradiated mice are accompanied by changed synaptic plasticity, adult neurogenesis and neuroinflammation.
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DOI：
10.1186/1750-1326-9-57
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发表时间：
2014-12-16
影响因子：
15.1
通讯作者：
Tapio S
中科院分区：
文献类型：
--
作者：
Kempf SJ;Casciati A;Buratovic S;Janik D;von Toerne C;Ueffing M;Neff F;Moertl S;Stenerlöw B;Saran A;Atkinson MJ;Eriksson P;Pazzaglia S;Tapio S
流行病学证据表明，如果在年轻时受到低剂量电离辐射（≤1.0戈伊）的照射，就会造成认知能力的持久改变。这种改变的机制尚不清楚。我们在分子和细胞水平上研究了低剂量全身γ辐射对脑暴露NMRI小鼠的长期影响，以阐明神经退行性变。在单次0.5或1.0戈伊照射后2个月和4个月观察到自发行为的显著变化。照射后6-7个月，在海马、齿状回（DG）和皮质中分析了脑蛋白质组、转录组和几种miRNA的变化。与突触肌动蛋白重塑相关的信号通路如Rac 1-Cofilin通路在皮质和海马中发生改变。此外，突触蛋白MAP-2和PSD-95增加DG和海马（1.0戈伊）。在1.0戈伊剂量下，海马和皮层中的突触可塑性基因Arc、c-Fos和CREB的表达持续下降。这些变化通过增加microRNA（miR-132/miR-212、miR-134）水平与表观遗传调节相关联。星形胶质细胞增生、胰岛素-生长因子/胰岛素信号传导的激活和小胶质细胞因子TNFα水平的增加表明辐射诱导的神经炎症。此外，成年DG内的神经发生持续受到负面影响照射后，特别是在1.0戈伊。这些数据表明，成年人在年轻时受到低剂量和中等剂量的辐射，可能会诱发神经认知障碍。这引起了人们对辐射安全标准和监管做法的关切。本文的在线版本（doi：10.1186/1750-1326-9-57）包含补充材料，可供授权用户使用。
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. The online version of this article (doi:10.1186/1750-1326-9-57) contains supplementary material, which is available to authorized users.
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影响因子：
4.7
作者：
Grinberg YY;van Drongelen W;Kraig RP
通讯作者：
Kraig RP
影响因子：
1.7
作者：
Bakshi, Mayur V.;Barjaktarovic, Zarko;Tapio, Soile
通讯作者：
Tapio, Soile
影响因子：
3.5
作者：
Impey, Soren;Davare, Monika;Lasiek, Adam;Fortin, Dale;Ando, Hideaki;Varlamova, Olga;Obrietan, Karl;Soderling, Thomas R.;Goodman, Richard H.;Wayman, Gary A.
通讯作者：
Wayman, Gary A.
DOI：
10.1073/pnas.0610059104
发表时间：
2007-01-09
影响因子：
11.1
作者：
Diana, Giovanni;Valentini, Giovanni;Fiorentini, Carla
通讯作者：
Fiorentini, Carla
影响因子：
5.4
作者：
GROVES P M;THOMPSON R F
通讯作者：
THOMPSON R F