title: Interleukin-1 receptor (IL-1R) mediates epilepsy-induced sleep disruption.
abstract: Sleep disruptions are common in epilepsy patients. Our previous study demonstrates that homeostatic factors and circadian rhythm may mediate epilepsy-induced sleep disturbances when epilepsy occurs at different zeitgeber hours. The proinflammatory cytokine, interleukin-1 (IL-1), is a somnogenic cytokine and may also be involved in epileptogenesis; however, few studies emphasize the effect of IL-1 in epilepsy-induced sleep disruption. We herein hypothesized that IL-1 receptor type 1 (IL-1R1) mediates the pathogenesis of epilepsy and epilepsy-induced sleep disturbances. We determined the role of IL-1R1 by using IL-1R1 knockout (IL-1R1 -/- KO) mice.
  
  
  
  Our results elucidated the decrease of non-rapid eye movement (NREM) sleep during the light period in IL-1R -/- mice and confirmed the somnogenic role of IL-1R1. Rapid electrical amygdala kindling was performed to induce epilepsy at the particular zeitgeber time (ZT) point, ZT13. Our results demonstrated that seizure thresholds induced by kindling stimuli, such as the after-discharge threshold and successful kindling rates, were not altered in IL-1R -/- mice when compared to those obtained from the wildtype mice (IL-1R +/+ mice). This result suggests that IL-1R1 is not involved in kindling-induced epileptogenesis. During sleep, ZT13 kindling stimulation significantly enhanced NREM sleep during the subsequent 6 h (ZT13-18) in wildtype mice, and sleep returned to the baseline the following day. However, the kindling-induced sleep alteration was absent in the IL-1R -/- KO mice.
  
  
  
  These results indicate that the IL-1 signal mediates epilepsy-induced sleep disturbance, but dose not participate in kindling-induced epileptogenesis.
authors.affiliation: Department of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4., Roosevelt Road, Taipei, 106, Taiwan.
authors.forename: Tzu-Rung
authors.initials: TR
authors.lastname: Huang
authors.affiliation: Department of Neurology, Mackay Memorial Hospital and Mackay Medical College, Taipei, Taiwan.
authors.forename: Shuo-Bin
authors.initials: SB
authors.lastname: Jou
authors.affiliation: Department of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4., Roosevelt Road, Taipei, 106, Taiwan.
authors.forename: Yu-Ju
authors.initials: YJ
authors.lastname: Chou
authors.affiliation: Department of Sport Management, College of Tourism, Leisure and Sports, Aletheia University, New Taipei City, Taiwan. pyi67@hotmail.com.
authors.forename: Pei-Lu
authors.initials: PL
authors.lastname: Yi
authors.affiliation: Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei, Taiwan.
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Department of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University, No. 1, Sec. 4., Roosevelt Road, Taipei, 106, Taiwan. fchang@ntu.edu.tw.|Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan. fchang@ntu.edu.tw.|Graduate Institute of Acupuncture Science, College of Chinese Medicine, China Medical University, Taichung, Taiwan. fchang@ntu.edu.tw.
authors.forename: Fang-Chia
authors.initials: FC
authors.lastname: Chang
mesh_terms: D000679:Amygdala / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004558:Electric Stimulation; D000069280:Electrocorticography; D004567:Electrodes, Implanted; D004827:Epilepsy / Q000150:complications* / Q000378:metabolism*; D060005:Genotyping Techniques; D007696:Kindling, Neurologic / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics / Q000378:metabolism*; D012640:Seizures / Q000209:etiology / Q000378:metabolism; D012890:Sleep / Q000502:physiology; D012893:Sleep Wake Disorders / Q000209:etiology* / Q000378:metabolism*
chemical_list: C583355:IL1R1 protein, mouse; D053573:Receptors, Interleukin-1 Type I
keywords: Amygdala; Epilepsy; IL-1 receptor; Kindling; Sleep