Increased expression of the lysosomal protease cathepsin S in hippocampal microglia following kainate-induced seizures
Increased expression of the lysosomal protease cathepsin S in hippocampal microglia following kainate-induced seizures
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DOI：
10.1016/j.neulet.2007.10.007
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发表时间：
2007-12-18
影响因子：
2.5
通讯作者：
Ishii, Isao
中科院分区：
文献类型：
--
作者：
Akahoshi, Noriyuki;Murashima, Yoshiya L.;Ishii, Isao
为了研究癫痫发作在发育中的大脑造成的损伤，通过向幼年小鼠腹腔注射红藻氨酸和尼古丁来诱导癫痫发作。一周后，用组织化学方法检查全脑切片，并用DNA芯片分析新皮质和海马区的基因表达谱。碘化丙啶和荧光素C染色显示，红藻氨酸可引起海马锥体神经元变性，而尼古丁不能。对芯片上12,488个探针组的比较分析表明，分别有208和1243个探针组在注射海人酸组小鼠的新皮质和海马区表达差异，在注射尼古丁的小鼠新皮质和海马区分别有和436个探针组的差异表达，变化模式主要是药物特异性和区域特异性的。在红藻氨酸修饰的多种基因中，包括代表神经退行性变和星形胶质细胞的基因，我们发现在红藻氨酸注射的小鼠的海马区，溶酶体半胱氨酸蛋白酶组织蛋白S的基因表达增加。海马匀浆的蛋白质印迹分析显示，海人藻氨酸诱导组织蛋白酶S的表达增加3.3倍。应用细胞类型特异性标记的免疫组织化学方法显示，组织蛋白酶S在小胶质细胞中表达，特别是在变性锥体神经元周围的小胶质细胞中表达，而在神经元本身和星形胶质细胞中不表达。在海人酸组小鼠的海马区CA1区。这些结果表明，红藻氨酸诱导的癫痫发作可引起神经变性、星形胶质细胞增生。而尼古丁诱导的微激活则不伴有组织蛋白S的表达。(C)2007爱思唯尔爱尔兰有限公司。保留所有权利。
To examine lesions caused by seizures in the developing brain, seizures were induced by the intraperitoneal injection of kainate and nicotine into juvenile mice. After a week, whole brain sections were examined using histochemistry and the gene expression profiles in the neocortices and hippocampi were analyzed using a DNA microarray. Propidium iodide and Fluoro-Jade C staining revealed that kainate but not nicotine-induced degeneration of the hippocampal pyramidal neurons. Comparative analyses of 12,488 probe sets on the microarray chip revealed the differential expression of 208 and 1243 probe sets in the neocortices and hippocampi of kainate-injected mice, respectively, as well as that of 535 and 436 probe sets in the neocortices and hippocampi of nicotine-injected mice, respectively, the patterns of change were largely drug-specific and region-specific. Among a variety of kainate-modified genes including those representing neurodegeneration and astrogliosis, we identified an increased gene expression of the lysosomal cysteine protease cathepsin S in the hippocampi of kainate-injected mice. Western blot analysis of the hippocampal homogenates revealed that kainate induced a 3.3-fold increase in cathepsin S expression. Immunohistochemistry using cell type-specific markers showed that cathepsin S was induced in microglia, especially those surrounding degenerating pyramidal neurons, but not in neurons themselves or astroglia. in the hippocampal CA1 region of kainate-injected mice. These results indicate that seizures induced by kainate elicit neurodegeneration, astrogliosis. and microalial activation accompanied by the expression of cathepsin S while those induced by nicotine do not. (C) 2007 Elsevier Ireland Ltd. All rights reserved.