Early detachment of neuromuscular junction proteins in ALS mice with SODG93A mutation
Early detachment of neuromuscular junction proteins in ALS mice with SODG93A mutation
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DOI：
10.4081/ni.2009.e16
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发表时间：
2009-01-01
影响因子：
3
通讯作者：
Abe, Koji
中科院分区：
文献类型：
--
作者：
Narai, Hisashi;Manabe, Yasuhiro;Abe, Koji
铜/锌超氧化物歧化酶（SOD!）突变的转基因动物DNA发展为麻痹性运动神经元疾病，类似于人类肌萎缩侧索硬化症（ALS）患者，通常用作ALS的模型。在人类SOD1基因G93A突变的转基因（Tg）小鼠（SOD1（小鼠））中，腹根轴突和肌肉与运动神经元之间的突触的缺失表明运动神经元的变性可能以死背变性模式进行。为了揭示SOD1小鼠轴突变性与肌肉萎缩进展之间的关系，我们研究了沿疾病进展的神经肌肉连接处的状态。作为神经肌肉连接（NMJ）的突触前或突触后标记物。本研究选用抗突触囊泡蛋白2 （anti-SV2）抗体和cz-bungarotoxin （α - butx）抗体，并选用抗agrin抗体作为突触裂的标志物。在CZBuTX和抗sv2抗体的免疫组化中，随着时间的推移，Tg小鼠双阳性NMJs在α - butx单阳性中的百分比下降。Tg小鼠突触后乙酰胆碱受体（AChR）簇数即使在晚期也未减少。免疫组化（Y - BuTX）和抗agrin抗体显示，从10周龄开始，Tg小鼠肌纤维周围抗agrin抗体免疫阳性面积增加。在这项研究中，我们发现Tg小鼠的神经末梢脱离开始于10周。两组小鼠的AChR水平在5-20周龄期间没有变化。AChR仍在NMJs聚集，提示肌肉异常是神经末梢脱离的结果。
The transgenic animals with mutant copper/zinc superoxide dismutase (SOD!) DNA develop paralytic motor neuron disease resembling human amyotrophic lateral sclerosis (ALS) patients and are commonly used as models for ALS. In the transgenic (Tg) mice with the G93A mutation of the human SOD1gene (SOD1(mice)), the loss of ventral root axons and the synapses between the muscles and the motor neurons suggested that the motor neuron degeneration might proceed in a dying back degeneration pattern. To reveal the relationship between axonal degeneration and the progression of the muscle atrophy in the SOD1,, mice we investigated the status of the neuromuscular junction along the disease progression. As a presynaptic or postsynaptic marker of neuromuscular junction (NMJ). anti-synaptic vesicle protein 2 (anti-SV2) antibody and cz-bungarotoxin (alpha-BuTX) were chosen in this study and as a marker of synaptic cleft, anti-agrin antibody was chosen in this study. In the immunohistochemistry of CZBuTX and anti-SV2 antibody the percentages of double positive NMJs among alpha-BuTX single positive were decreased in Tg mice through time from ten weeks. The number of postsynaptic acethylcholine receptor (AChR) clusters did not decrease in Tg mice even at the end stage. Immunohistochemistry of (Y BuTX and anti-agrin antibody revealed that the increase of immunopositive area of anti-agrin antibody around the muscle fiber in Tg mice from ten weeks of age. In this study, we revealed that the detachment of nerve terminals started at ten weeks in Tg mice. The levels of AChR did not change throughout 5-20 weeks of age in both groups of mice. and AChR remains clustering at NMJs, suggesting that the muscle abnormality is the result of detachment of nerve terminals.