NLRP3 Inflammasome Activation Leads to Epileptic Neuronal Apoptosis

Abstract

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.

Keywords: Epilepsy; MCC950; NLRP3 inflammasome; apoptosis; inflammation; neuron..