Parvalbumin and calbindin D-28k immunoreactivity in transgenic mice with a G93A mutant SOD1 gene
Parvalbumin and calbindin D-28k immunoreactivity in transgenic mice with a G93A mutant SOD1 gene
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DOI：
10.1016/j.brainres.2006.01.129
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发表时间：
2006-04
期刊：
影响因子：
2.9
通讯作者：
S. Sasaki;H. Warita;T. Komori;T. Murakami;K. Abe;M. Iwata
中科院分区：
文献类型：
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作者：
S. Sasaki;H. Warita;T. Komori;T. Murakami;K. Abe;M. Iwata
进行免疫组织化学研究以检查钙结合蛋白是否参与携带G93 A突变人SOD 1基因的转基因小鼠脑干和脊髓运动神经元的变性。来自年龄匹配的非转基因野生型小鼠的样本作为对照。在对照组的脊髓中，小白蛋白免疫反应神经元的密度在脊髓中的大前角神经元中最高，在后角神经元中较低。另一方面，钙结合蛋白D-28 k免疫反应性比用小清蛋白抗血清观察到的明显得多。Rexed的板II密集的钙结合蛋白D-28 k免疫染色，而在前角，钙结合蛋白-D-28 k阳性的小神经元几乎分散在一个分散的模式。在转基因小鼠中，小白蛋白阳性前角神经元严重减少，即使在前症状阶段，而钙结合蛋白阳性神经元在很大程度上保留。在症状阶段，小清蛋白和钙结合蛋白D-28 k免疫反应性显着减少或消失在前角。免疫印迹分析显示，与对照组相比，转基因小鼠对小清蛋白抗体的免疫反应性显着降低。在脑干中，小清蛋白阳性的眼神经元和外展神经元和钙结合蛋白D-28 k阳性的第六核在转基因小鼠和对照中保存良好。因此，弥漫性和严重损失的小白蛋白免疫反应的大运动神经元，甚至在早期阶段，在SOD 1转基因小鼠和钙结合蛋白D-28 k免疫反应的正常大运动神经元的情况下，这些钙结合蛋白可能有助于选择性的脆弱性和早期丧失功能的大运动神经元在此SOD 1转基因小鼠模型。
Immunohistochemical study was performed to examine if calcium-binding proteins are involved in the degeneration of motor neurons in the brain stems and the spinal cords of transgenic mice carrying a G93A mutant human SOD1 gene. Specimens from age-matched non-transgenic wild-type mice served as controls. In the spinal cord of the controls, the density of parvalbumin-immunoreactive neurons was highest in the large anterior horn neurons and lower in the posterior horn neurons in the spinal cord. On the other hand, calbindin D-28k immunoreactivity was much less apparent than that observed with parvalbumin antisera. Rexed's lamina II was densely immunostained for calbindin D-28k, whereas, in the anterior horn, calbindin-D-28k-positive small neurons were barely dispersed in a scattered pattern. In transgenic mice, parvalbumin-positive anterior horn neurons were severely reduced, even at the presymptomatic stage, whereas calbindin-positive neurons were largely preserved. At the symptomatic stage, both parvalbumin and calbindin D-28k immunoreactivity markedly diminished or disappeared in the anterior horn. Immunoblotting analysis revealed a significant reduction of immunoreactivity to parvalbumin antibody in transgenic mice compared with the controls. In the brain stem, parvalbumin-positive oculomotor and abducens neurons and the calbindin D-28k-positive sixth nucleus were well-preserved in transgenic mice as well as in the controls. Thus, the diffuse and severe loss of parvalbumin immunoreactivity of large motor neurons even at early stages in SOD1-transgenic mice and the absence of calbindin D-28k immunoreactivity of normal large motor neurons suggest that these calcium-binding proteins may contribute to selective vulnerability and an early loss of function of large motor neurons in this SOD1-transgenic mouse model.