title: The effect of IL-1β on synaptophysin expression and electrophysiology of hippocampal neurons through the PI3K/Akt/mTOR signaling pathway in a rat model of mesial temporal lobe epilepsy.
abstract: BACKGROUND
  The inflammation induced by interleukin-1β (IL-1β) is a critical factor in the pathogenesis of mesial temporal lobe epilepsy (MTLE). Synaptophysin (SYN) and other changes, including neuron electrophysiology, participate in the pathophysiological processes of MTLE. Phosphatidylinositol 3-kinase (PI3K)/Akt/ mammalian target of rapamycin (mTOR) signaling pathway may play a critical role in regulating SYN expression and electrophysiology of hippocampal neurons.
  
  
  METHODS
  We used lithium-pilocarpine-treated rats as model of human MTLE, detecting epileptic seizures with digital video-EEG, and evaluating the proteins related to the PI3K/Akt/mTOR signaling pathway by western blot (WB). Then, we cultured primary neuron and established a neuronal epilepsy model using Mg2+-free media. Immunocytochemistry and WB were used to investigate SYN expression, and whole-cell current clamp recording techniques were used to detect the electrophysiological properties of cultured neurons.
  
  
  RESULTS
  We have demonstrated that IL-1β can activate the PI3K/Akt/mTOR signaling pathway in primary hippocampal neurons, and we speculate that IL-1β may affect SYN expression and neuron electrophysiology through PI3K/Akt/mTOR signaling pathway.
  
  
  CONCLUSIONS
  We confirmed that IL-1β stimulated SYN expression and epileptiform discharges, and that blocking the PI3K/Akt/mTOR pathway alleviated these phenomena. Therefore, activation of the PI3K/Akt/mTOR signaling pathway by IL-1β contributes to the pathogenesis of MTLE, and modulating this pathway is a promising strategy of study for therapies to prevent or reverse the cellular and molecular mechanisms of epileptogenesis in MTLE.
authors.affiliation: a Department of Pediatrics , Xiangya Hospital of Central South University , Changsha , China.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: a Department of Pediatrics , Xiangya Hospital of Central South University , Changsha , China.|b Hunan Intellectual and Developmental Disabilities Research Center of Children , Changsha , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Peng
authors.affiliation: a Department of Pediatrics , Xiangya Hospital of Central South University , Changsha , China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Wu
authors.affiliation: a Department of Pediatrics , Xiangya Hospital of Central South University , Changsha , China.
authors.forename: Ahmed
authors.identifier: http://orcid.org/0000-0002-6917-6480
authors.initials: A
authors.lastname: Arafat
authors.affiliation: a Department of Pediatrics , Xiangya Hospital of Central South University , Changsha , China.|b Hunan Intellectual and Developmental Disabilities Research Center of Children , Changsha , China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yin
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D018020:Lithium Compounds; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010862:Pilocarpine; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D016708:Synaptophysin / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D018020:Lithium Compounds; D019869:Phosphatidylinositol 3-Kinases; D010862:Pilocarpine; D051057:Proto-Oncogene Proteins c-akt; D016708:Synaptophysin; D058570:TOR Serine-Threonine Kinases; C000594089:IL1B protein, rat; C569016:Syp protein, rat; C546845:mTOR protein, rat
keywords: IL-1β; Inflammation; MTLE; SYN; electrophysiology