Radiation-induced reductions in neurogenesis are ameliorated in mice deficient in CuZnSOD or MnSOD.

Radiation-induced reductions in neurogenesis are ameliorated in mice deficient in CuZnSOD or MnSOD.
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DOI:
10.1016/j.freeradbiomed.2009.08.016
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发表时间:
2009-11-15
影响因子:
7.4
通讯作者:
Fike, John R.
Fike, John R.
中科院分区:
医学1区
文献类型:
--
作者:
Fishman, Kelly;Baure, Jennifer;Zou, Yani;Huang, Ting-Ting;Andres-Mach, Marta;Rola, Radoslaw;Suarez, Tatiana;Acharya, Munjal;Limoli, Charles L.;Lamborn, Kathleen R.;Fike, John R.

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电离辐射显着影响海马神经发生,并与认知功能障碍,这些影响可能会受到改变微环境。氧化应激是一个影响神经发生的因素,而应对这种应激的保护途径之一涉及抗氧化酶超氧化物歧化酶(SOD)。本研究探讨了细胞质(SOD1)或线粒体(SOD2)SOD的缺乏如何影响海马神经发生的辐射效应。野生型(WT)、SOD 1和SOD 2敲除(KO)小鼠接受5戈伊的单次X射线剂量,2个月后对齿状颗粒下区中新产生的细胞的存活和表型命运进行定量。辐射暴露减少WT小鼠的神经发生,但在KO小鼠中没有明显的影响,尽管在照射前两种SOD KO品系的神经发生基线水平降低。此外,WT和两种KO菌株之间在辐射如何影响新生成的星形胶质细胞和活化的小胶质细胞方面存在显著差异。造成这些影响的机制尚不清楚,但一项初步体外研究表明,超氧化物水平升高具有“保护”作用。总的来说,这些数据表明,在SOD缺乏的条件下,有一个共同的途径决定了神经发生是如何受到电离辐射的影响。
Ionizing irradiation significantly affects hippocampal neurogenesis and is associated with cognitive impairments; these effects may be influenced by an altered microenvironment. Oxidative stress is a factor that has been shown to affect neurogenesis, and one of the protective pathways to deal with such stress involves the antioxidant enzyme superoxide dismutase (SOD). This study addressed how the deficiency of cytoplasmic (SOD1) or mitochondrial (SOD2) SOD impacts radiation effects on hippocampal neurogenesis. Wild type (WT), SOD 1 and SOD2 knock out (KO) mice received a single x-ray dose of 5 Gy, and quantification of the survival and phenotypic fate of newly generated cells in the dentate subgranular zone was performed 2 months later. Radiation exposure reduced neurogenesis in WT mice but had no apparent effect in KO mice, although baseline levels of neurogenesis were reduced in both SOD KO strains prior to irradiation. Additionally, there were marked and significant differences between WT and both KO strains in how irradiation affected newly generated astrocytes and activated microglia. The mechanism(s) responsible for these effects are not yet known, but a pilot in vitro study suggests a ‘protective’ effect of elevated levels of superoxide. Overall, these data suggest that under conditions of SOD deficiency, there is a common pathway dictating how neurogenesis is affected by ionizing irradiation.
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发表时间: 2005-07-01
影响因子: 5.3
作者:
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发表时间: 2009-04
影响因子: 3.5
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期刊: OXIDATIVE/ENERGY METABOLISM IN NEURODEGENERATIVE DISORDERS
影响因子: --
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