Deregulated expression of cytoskeleton related genes in the spinal cord and sciatic nerve of presymptomatic SOD1(G93A) Amyotrophic Lateral Sclerosis mouse model.

Deregulated expression of cytoskeleton related genes in the spinal cord and sciatic nerve of presymptomatic SOD1(G93A) Amyotrophic Lateral Sclerosis mouse model.
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DOI:
10.3389/fncel.2014.00148
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发表时间:
2014
影响因子:
5.3
通讯作者:
Chadi G
Chadi G
中科院分区:
医学2区
文献类型:
--
作者:
Maximino JR;de Oliveira GP;Alves CJ;Chadi G

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肌萎缩侧索硬化症(ALS)中与细胞骨架相关的早期分子事件,特别是为运动神经元提供强营养支持的雪旺细胞(SC)中的细胞骨架,描述得很少。注释、可视化和集成发现数据库(大卫)工具通过在症状前SOD1G93A小鼠的腰脊髓和坐骨神经的大基因谱分析中采用细胞组分本体(CCO)来鉴定细胞凋亡相关基因。分别从40日龄(肌动蛋白细胞骨架)和80日龄(微管细胞骨架、细胞骨架部分、肌动蛋白细胞骨架、神经丝细胞骨架和细胞骨架)转基因小鼠的脊髓失调基因中描述了1个和5个与细胞骨架相关的CCO术语。此外,从60天龄转基因坐骨神经的失调基因中描述了四个术语(肌动蛋白细胞骨架、细胞骨架部分、微管细胞骨架和细胞骨架)。Kif1b是唯一的失调基因在多个研究区域或症状前年龄。Kif1b [定量聚合酶链反应(qPCR)]的表达在症状前ALS小鼠的腰髓(40天龄)中升高,在坐骨神经(60天龄)中降低,结果与微阵列结果一致。上调(24.8倍)Kif1b的激光显微切割富集免疫标记的运动神经元从40天龄的症状前SOD1G93A小鼠的脊髓。此外,Kif1b在症状前ALS小鼠(60日龄)的坐骨神经雪旺细胞中下调,这些雪旺细胞通过细胞显微切割(6.35倍)、细胞分选(3.53倍)和原代培养(2.70倍)技术富集。细胞骨架分子的基因调控是ALS症状前阶段运动神经元和雪旺细胞中的重要事件,并且可能与神经元死亡的死亡机制有关。此外,脊髓和坐骨神经细胞中Kif1b的差异调节成为ALS的关键事件。
Early molecular events related to cytoskeleton are poorly described in Amyotrophic Lateral Sclerosis (ALS), especially in the Schwann cell (SC), which offers strong trophic support to motor neurons. Database for Annotation, Visualization and Integrated Discovery (DAVID) tool identified cytoskeleton-related genes by employing the Cellular Component Ontology (CCO) in a large gene profiling of lumbar spinal cord and sciatic nerve of presymptomatic SOD1G93A mice. One and five CCO terms related to cytoskeleton were described from the spinal cord deregulated genes of 40 days (actin cytoskeleton) and 80 days (microtubule cytoskeleton, cytoskeleton part, actin cytoskeleton, neurofilament cytoskeleton, and cytoskeleton) old transgene mice, respectively. Also, four terms were depicted from the deregulated genes of sciatic nerve of 60 days old transgenes (actin cytoskeleton, cytoskeleton part, microtubule cytoskeleton and cytoskeleton). Kif1b was the unique deregulated gene in more than one studied region or presymptomatic age. The expression of Kif1b [quantitative polymerase chain reaction (qPCR)] elevated in the lumbar spinal cord (40 days old) and decreased in the sciatic nerve (60 days old) of presymptomatic ALS mice, results that were in line to microarray findings. Upregulation (24.8 fold) of Kif1b was seen in laser microdissected enriched immunolabeled motor neurons from the spinal cord of 40 days old presymptomatic SOD1G93A mice. Furthermore, Kif1b was dowregulated in the sciatic nerve Schwann cells of presymptomatic ALS mice (60 days old) that were enriched by means of cell microdissection (6.35 fold), cell sorting (3.53 fold), and primary culture (2.70 fold) technologies. The gene regulation of cytoskeleton molecules is an important occurrence in motor neurons and Schwann cells in presymptomatic stages of ALS and may be relevant in the dying back mechanisms of neuronal death. Furthermore, a differential regulation of Kif1b in the spinal cord and sciatic nerve cells emerged as key event in ALS.
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发表时间: 2003-03-01
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