Institute of Biophysics, Biological Research Centre, Szeged. Hungary.
Department of Neurology, University of Szeged, Szeged. Hungary.
CNS Neurol Disord Drug Targets. 2017;16(3):356-367. doi: 10.2174/1871527315666161223130409.
Motoneurons with naturally elevated calcium binding protein content, such as parvalbumin, are more resistant against injury. Furthermore, increase of intracellular calcium, which plays a pivotal role in injury of neurons, could be moderated by elevating their calcium binding proteins.
To test whether by elevating parvalbumin content of motoneurons, activation of neighboring microglial cells, a robust component of the inflammatory reaction after injury, could be influenced.
Mice overexpressing neuronal parvalbumin were derived and the spinal motoneurons were challenged by cutting the sciatic nerve. At postoperative days 1, 4, 7, 14 and 21 the change of the chemokine ligand 2 immunostaining in the motoneurons and the activation of microglial cells, measured as alterations in CD11b immunostaining were determined. Calcium level of motoneurons was tested electron microscopically at postoperative day 7.
After axotomy, increased level of chemokine ligand 2 was detected in the lumbar motoneurons. The staining intensity reached its maximum at day 7 and decayed faster in transgenic mice compared to controls. Microglial activation around motoneurons attenuated faster in parvalbumin overexpressing mice, too, but the decrease of microglial activation was delayed compared to the decline of the chemokine ligand 2 signal. At the time when the microglial reaction peaked, no intracellular calcium increase was detected in the motoneurons of transgenic mice, in contrast to the twofold increase in wild type animals.
Increased calcium buffering capacity, which augments resistance of motoneurons against calcium-mediated injury, leads to earlier termination of motoneuronal emission of CCL2 followed by a reduction of neighboring microglial activation after axotomy.
自然表达高水平钙结合蛋白的运动神经元，如钙结合蛋白 4，对损伤具有更强的抗性。此外，通过增加钙结合蛋白，细胞内钙的增加（神经元损伤的关键因素）可以得到调节。
研究通过提高运动神经元中的钙结合蛋白 parvalbumin 的含量，是否可以影响损伤后炎症反应中活跃的邻近小胶质细胞的激活。
构建神经元过表达 parvalbumin 的小鼠模型，并通过切断坐骨神经来挑战脊髓运动神经元。在术后第 1、4、7、14 和 21 天，通过检测趋化因子配体 2 的免疫染色变化以及小胶质细胞的激活（通过 CD11b 免疫染色的改变来衡量），来评估运动神经元的变化。在术后第 7 天，通过电子显微镜测试运动神经元的钙水平。
在轴突切断后，腰段运动神经元中检测到趋化因子配体 2 水平升高。其染色强度在第 7 天达到最大值，并且在转基因小鼠中比对照小鼠衰减更快。过表达 parvalbumin 的小鼠中，小胶质细胞在运动神经元周围的激活也更快衰减，但与趋化因子配体 2 信号的下降相比，小胶质细胞激活的下降被延迟。当小胶质细胞反应达到峰值时，在转基因小鼠的运动神经元中没有检测到细胞内钙增加，而在野生型动物中则增加了两倍。
增加钙缓冲能力，增强运动神经元对钙介导损伤的抗性，导致 CCL2 运动神经元发射的更早终止，随后轴突切断后邻近小胶质细胞的激活减少。
