title: Interleukin-1β Plays a Pivotal Role via the PI3K/Akt/mTOR Signaling Pathway in the Chronicity of Mesial Temporal Lobe Epilepsy.
abstract: 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-1β (IL-1β) level is involved in the epileptogenesis of MTLE, and we further investigated how it works in its chronicity in this study.
  
  
  
  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.
  
  
  
  We revealed that mTOR is continuously activated in the rat MTLE model and children with MTLE, and it correlated with the IL-1β level. We further proved that IL-1β activates neurons via the PI3K/Akt/mTOR signaling pathway, accompanied by the upregulation of MAP2 and the enhancement of SVE in hippocampal neurons.
  
  
  
  Our findings suggest that IL-1β 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.
authors.affiliation: Department of Pediatrics, Xiangya Hospital of Central South University, Changsha, China.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Xiao
authors.forename: Jing
authors.initials: J
authors.lastname: Peng
authors.forename: Na
authors.initials: N
authors.lastname: Gan
authors.forename: Ahmed
authors.initials: A
authors.lastname: Arafat
authors.forename: Fei
authors.initials: F
authors.lastname: Yin
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002478:Cells, Cultured; D002648:Child; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D018721:Muscarinic Agonists / Q000633:toxicity; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D004791:Enzyme Inhibitors; D053583:Interleukin-1beta; D018721:Muscarinic Agonists; D010862:Pilocarpine; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D003975:Diazepam; D020123:Sirolimus
keywords: Interleukin-1β; Mammalian target of rapamycin; Mesial temporal lobe epilepsy; Synaptic vesicle endocytosis