Journal of Neuroinflammation | |
NLRP1 inflammasome is activated in patients with medial temporal lobe epilepsy and contributes to neuronal pyroptosis in amygdala kindling-induced rat model | |
Lan Tan3  Jin-Tai Yu2  Meng-Meng Li5  Zhen Sun5  Ying Li4  Xiang-Fei Meng5  Teng Jiang3  Da-Wei Meng6  Hua Chen4  Meng-Shan Tan1  Jian-Guo Zhang6  Chen-Chen Tan5  | |
[1] College of Medicine and Pharmaceutics, Ocean University of China, No.5 Yushan Road, Qingdao 266003, China;Memory and Aging Center, Department of Neurology, University of California, San Francisco 94158, CA, USA;Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, No.5 Donghai Middle Road, Qingdao 266071, China;Department of Pathology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao 266071, China;Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, No.5 Donghai Middle Road, Qingdao 266071, China;Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No.6, Tiantan Xili, Beijing 100050, China | |
关键词: temporal lobe epilepsy; Caspase-1; inflammasome; pyroptosis; NLRP1; | |
Others : 1149679 DOI : 10.1186/s12974-014-0233-0 |
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received in 2014-10-21, accepted in 2014-12-28, 发布年份 2015 | |
【 摘 要 】
Background
Temporal lobe epilepsy (TLE) is often characterized pathologically by severe neuronal loss in the hippocampus. Understanding the mechanisms of neuron death is key to preventing the neurodegeneration associated with TLE. However, the involvement of neuronal loss to the epileptogenic process has yet to be fully determined. Recent studies have shown that the activation of NLRP1 can generate a functional caspase-1-containing inflammasome in vivo to drive the proinflammatory programmed cell death termed ‘pyroptosis’, which has a key role in the pathogenesis of neurological disorders. To the best of our knowledge, there are no reported studies that performed detailed identification and validation of NLRP1 inflammasome during the epileptogenic process.
Methods
We first compared expression of NLRP1 and caspase-1 in resected hippocampus from patients with intractable mesial temporal lobe epilepsy (mTLE) with that of matched control samples. To further examine whether the activation of NLRP1 inflammasome contributes to neuronal pyroptosis, we employed a nonviral strategy to knock down the expression of NLRP1 and caspase-1 in the amygdala kindling-induced rat model. Proinflammatory cytokines levels and hippocampal neuronal loss were evaluated after 6 weeks of treatment in these NLRP1 or caspase-1 deficiency TLE rats.
Results
Western blotting detected upregulated NLRP1 levels and active caspase-1 in mTLE patients in comparison to those levels seen in the controls, suggesting a role for this inflammasome in mTLE. Moreover, we employed direct in vivo infusion of nonviral small interfering RNA to knockdown NLRP1 or caspase-1 in the amygdala kindling-induced rat model, and discovered that these NLRP1 or caspase-1 silencing rats resulted in significantly reduced neuronal pyroptosis.
Conclusions
Our data suggest that NLRP1/caspase-1 signaling participates in the seizure-induced degenerative process in humans and in the animal model of TLE and points to the silencing of NLRP1 inflammasome as a promising strategy for TLE therapy.
【 授权许可】
2015 Tan et al.; licensee BioMed Central.
【 预 览 】
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