X Irradiation Changes Dendritic Spine Morphology and Density through Reduction of Cytoskeletal Proteins in Mature Neurons

X Irradiation Changes Dendritic Spine Morphology and Density through Reduction of Cytoskeletal Proteins in Mature Neurons
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X 辐射通过减少成熟神经元中的细胞骨架蛋白来改变树突棘形态和密度

DOI:
10.1667/rr3098.1
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发表时间:
2013
期刊:
The Journal of Clinical Investigation
影响因子:
--
通讯作者:
T. Nakano
T. Nakano
中科院分区:
--
文献类型:
--
作者:
K. Shirai;T. Mizui;Yoshiyuki Suzuki;M. Okamoto;K. Hanamura;Y. Yoshida;Mizuki Hino;S. Noda;W. Al;A. Chakravarti;T. Shirao;T. Nakano

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神经元是神经回路的重要组成部分,并提供大脑功能组织。我们以前报道过X射线照射诱导未成熟神经元凋亡。据我们所知,很少有报道调查的影响,X射线照射对成熟的神经元。我们分析了X射线照射对成熟神经元树突棘的形态、密度和细胞骨架蛋白的影响。采用Banker法制备了18天胚胎海马神经元。在体外21天的神经元以几个剂量进行X射线照射,并立即固定。为了评估树突棘形态和密度,用增强型绿色荧光蛋白(GFP)的报告质粒转染神经元。使用电子显微镜评价X射线照射导致的树突棘的变化。为了分析树突棘内的细胞骨架蛋白,我们进行了免疫细胞化学检测丝状肌动蛋白(F-actin),dreplatin和PSD-95。X射线照射立即改变树突棘的形态,和照射的棘显着更薄,更长的比未照射的棘。X射线照射以剂量依赖性方式降低树突棘密度。电子显微镜证实了X射线照射后树突棘的这些变化。免疫组织化学研究表明,X射线照射减少了树突棘内的drexine和F-肌动蛋白的积累,但不PSD-95。这些结果表明,X射线照射立即降低树突棘密度,并通过减少细胞骨架蛋白的丰度来改变成熟神经元的形态。异常树突棘可能与临床环境中X射线照射后的急性不良反应有关,尽管需要进一步的研究来验证这些发现。
Neurons are essential components of neural circuits and provide brain function organization. We previously reported that X irradiation induces apoptosis in immature neurons. To the best of our knowledge, there have been few reports investigating the effects of X irradiation on mature neurons. We analyzed the effects of X irradiation on the morphology, density and cytoskeletal proteins in dendritic spines on mature neurons. We prepared developing hippocampal neurons from 18 days embryo by using Banker's method. Neurons at 21 days in vitro were X irradiated at several doses and were immediately fixed. To evaluate the dendritic spine morphology and density, the neurons were transfected with a reporter plasmid for enhanced green fluorescent protein (GFP). Changes in the dendritic spines as a result of X irradiation were evaluated using electron microscopy. To analyze the cytoskeletal proteins within the dendritic spines, we performed immunocytochemistry to detect filamentous actin (F-actin), drebrin and PSD-95. X irradiation immediately changed the dendritic spine morphology, and the irradiated spines were significantly thinner and longer than the nonirradiated spines. X irradiation decreased the dendritic spine density in a dose-dependent manner. Electron microscopy confirmed these changes of dendritic spines by X irradiation. Immunohistochemical studies showed that X irradiation decreased the accumulation of drebrin and F-actin, but not PSD-95, within the dendritic spines. These results suggest that X irradiation immediately decreases the dendritic spine density and changes the morphology of mature neurons by reducing the abundance of cytoskeletal proteins. The abnormal dendritic spines may be associated with acute adverse effects after X irradiation in a clinical setting, although further investigations are warranted to validate these findings.
DOI: --
发表时间: 2003-07
期刊: Cancer research
影响因子: 11.2
作者:
S. Mizumatsu;Michelle Monje;Duncan R. Morhardt;R. Rola;T. Palmer;J. Fike
通讯作者: S. Mizumatsu;Michelle Monje;Duncan R. Morhardt;R. Rola;T. Palmer;J. Fike