Title:NLRP3 Inflammasome Activation Leads to Epileptic Neuronal Apoptosis
Volume: 15
Issue: 4
Author(s): Kai Shen, Quangao Mao, Xiaoqin Yin, Chunyan Zhang, Yi Jin, Aiqing Deng, Zhifeng Gu*Bohua Chen*
Affiliation:
- Department of Rheumatology, Affiliated Hospital of Nantong University, Nantong,China
- Department of Pharmacy, Affiliated Hospital of Nantong University, Nantong,China
Keywords:
Epilepsy, NLRP3 inflammasome, MCC950, inflammation, apoptosis, neuron.
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.