NLRP3 Inflammasome Activation Leads to Epileptic Neuronal Apoptosis.
NLRP3 Inflammasome Activation Leads to Epileptic Neuronal Apoptosis.
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DOI：
10.2174/1567202616666181122165540
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发表时间：
2019-01
影响因子：
2.1
通讯作者：
K. Shen;Q. Mao;Xiaoqin Yin;Chunyan Zhang;Yi Jin;Aiqing Deng;Z. Gu;Bohua Chen
中科院分区：
文献类型：
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作者：
K. Shen;Q. Mao;Xiaoqin Yin;Chunyan Zhang;Yi Jin;Aiqing Deng;Z. Gu;Bohua Chen
背景NOD样受体蛋白3（NLRP 3）炎性小体参与多种神经系统疾病，但其在癫痫中的作用仍需进一步研究。方法采用Western blot方法检测NLRP 3炎性小体和凋亡相关蛋白的表达。MTT用于评估细胞活力。通过Nissl染色，在NLRP 3敲除（KO）小鼠中进一步验证了NLRP 3炎性体在癫痫神经元凋亡中的作用。结果：无镁溶液处理后，SH-SY 5 Y细胞NLRP 3炎性小体表达增加，神经元凋亡增加。这种作用在用MCC 950作为常见的NLRP 3抑制剂处理的细胞中被抑制，从而暗示NLRP 3炎性体在癫痫神经元凋亡中的作用。在NLRP 3 KO小鼠中进一步证实了该发现的体内相关性。与野生型小鼠相比，在NLRP 3 KO小鼠中，戊四唑诱导的神经元损失被显著抑制。结论NLRP 3炎性小体与癫痫的发生发展存在相互作用。此外，MCC 950可能代表用于治疗NLRP 3炎性小体驱动的致癫痫活性的重要治疗药物。
BACKGROUND While the NOD-Like Receptor Protein-3 (NLRP3) inflammasome is involved in a variety of nervous system diseases, its role in epilepsy still needs to be further investigated. METHODS The expressions of NLRP3 inflammasome and apoptosis related proteins were examined by Western blot. MTT was used to assess cell viability. The role of NLRP3 inflammasome in epileptic neuronal apoptosis was further validated in NLRP3 knockout (KO) mice by Nissl staining. RESULTS Exposure of SH-SY5Y cells to free-Mg2+ solutions increased the expression of NLRP3 inflammasome with a concomitant increase in neuronal apoptosis. This effect was inhibited in cells treated with MCC950 as a common NLRP3 inhibitor, thereby implicating the role of NLRP3 inflammasome in epileptic neuronal apoptosis. In vivo relevance of this finding was further corroborated in the NLRP3 KO mice. Compared with the wild type mice, neuronal loss induced by pentylenetetrazole was significantly inhibited in the NLRP3 KO mice. CONCLUSION The study presented herein demonstrates the interaction between NLRP3 inflammasome and epilepsy progression. In addition, MCC950 might represent an important therapeutic drug for the treatment of NLRP3 inflammasome driven epileptogenic activity.