期刊
NEUROIMMUNOMODULATION
卷 23, 期 5-6, 页码 332-344出版社
KARGER
DOI: 10.1159/000460254
关键词
Mesial temporal lobe epilepsy; Synaptic vesicle endocytosis; Mammalian target of rapamycin; Interleukin-1 beta
资金
- National Natural Science Foundation of China [81371434, 81171226]
Objective: Mesial temporal lobe epilepsy (MTLE) is the most common type of refractory epilepsy. It is often associated with hippocampal sclerosis, which is histopathologically characterized by selective neuron loss, mossy fiber sprouting, and synapse reconstruction, and is the primary cause of refractory epilepsy. Its mechanism has not been fully elucidated. Substantial evidence now supports that inflammatory pathways are activated in epilepsy foci. We have confirmed that the interleukin-1 beta (IL-1 beta) level is involved in the epileptogenesis of MTLE, and we further investigated how it works in its chronicity in this study. Methods: The MTLE model was induced by pilocarpine, and Western blot and co-immunoprecipitation were used to detect proteins related to the PI3K/Akt/mammalian target of rapamycin (mTOR) signaling pathway in the hippocampi of MTLE rats and MTLE children. Meanwhile, primary hippocampal neurons were cultured and transfected by lentivirus, and the same methods were used to test the related protein expression; fluorescent dye FM4-64 was used to measure synaptic vesicle endocytosis (SVE) of neurons. Results: We revealed that mTOR is continuously activated in the rat MTLE model and children with MTLE, and it correlated with the IL-1 beta level. We further proved that IL-1 beta activates neurons via the PI3K/Akt/mTOR signaling pathway, accompanied by the upregulation of MAP2 and the enhancement of SVE in hippocampal neurons. Conclusion: Our findings suggest that IL-1 beta can activate mTOR, followed by activated neurons, which is critical in the pathogenesis of MTLE chronicity. These findings contribute to the understanding of the pathogenesis of MTLE, and targeting inflammation modulators in MTLE may provide new pathways for therapy of refractory epilepsy. (C) 2017 S. Karger AG, Basel
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