Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis
Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis
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DOI：
10.1046/j.1471-4159.2001.00582.x
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发表时间：
2001-11-01
影响因子：
4.7
通讯作者：
Appel, SH
中科院分区：
文献类型：
--
作者：
Beers, DR;Ho, BK;Appel, SH
在肌萎缩侧索硬化症（ALS）的免疫介导以及转基因模型中，脆弱的脊髓运动神经元细胞内钙增加。为了确定细胞内钙水平是否受到钙结合蛋白小清蛋白的影响，我们开发了在脊髓运动神经元中过表达小清蛋白的转基因小鼠。ALS免疫球蛋白。在对照动物中，增加了运动神经元末梢的细胞内钙和自发性递质释放，但在小清蛋白过表达转基因小鼠中没有。与突变SOD 1（mSOD 1）转基因小鼠杂交的小白蛋白转基因小鼠，家族性ALS的动物模型，有显着减少运动神经元的损失，并延迟疾病发作（17%）和延长生存期（11%）相比，只有mSOD 1转基因小鼠。这些结果证实了钙结合蛋白小清蛋白在改变运动神经元钙稳态中的重要性。增加的运动神经元小清蛋白可以显著减弱免疫介导的钙增加，并在较小程度上补偿转基因小鼠中mSOD 1介导的“毒性获得功能”。
Intracellular calcium is increased in vulnerable spinal motoneurons in immune-mediated as well as transgenic models of amyotrophic lateral sclerosis (ALS). To determine whether intracellular calcium levels are influenced by the calcium-binding protein parvalbumin, we developed transgenic mice overexpressing parvalbumin in spinal motoneurons. ALS immunoglobulins. increased intracellular calcium and spontaneous transmitter release at motoneuron terminals in control animals, but not in parvalbumin overexpressing transgenic mice. Parvalbumin transgenic mice interbred with mutant SOD1 (mSOD1) transgenic mice, an animal model of familial ALS, had significantly reduced motoneuron loss, and had delayed disease onset (17%) and prolonged survival (11%) when compared with mice with only the mSOD1 transgene. These results affirm the importance of the calcium binding protein parvalbumin in altering calcium homeostasis in motoneurons. The increased motoneuron parvalbumin can significantly attenuate the immune-mediated increases in calcium and to a lesser extent compensate for the mSOD1-mediated 'toxic-gain-of-function' in transgenic mice.