Interleukin-1 receptor (IL-1R) mediates epilepsy-induced sleep disruption

Abstract

BackgroundSleep 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.ResultsOur 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.ConclusionsThese results indicate that the IL-1 signal mediates epilepsy-induced sleep disturbance, but dose not participate in kindling-induced epileptogenesis.

Decoding Circadian Rhythm and Epileptic Activities: Clues From Animal Studies

“…The involvement of IL-1β in an altered sleep architecture in epilepsy is further verified by Huang et al They performed amygdaloid kindling stimulation at the particular ZT13 in both IL-1β receptor type 1 (IL-1R) KO mice and wildtype (WT) mice. In WT mice, kindling stimulation at ZT13 significantly enhanced NREM sleep, contrary to that observed in IL-1R KO mice ( 85 ). Yet no difference of seizure susceptibility between WT and KO mice were found.…”

Sleep Disruption Worsens Seizures: Neuroinflammation as a Potential Mechanistic Link

“…Furthermore, sleep deprivation synergized with epilepsy to elevate miR-146a expression, an important inflammatory modulator [326]. Compelling evidence indicates that the interleukin-1 receptor (IL-1R) mediates epilepsy-induced sleep disruption in IL-1R deficient mice, which exhibited less NREM sleep when compared to sufficiently rested counterparts [327]. However, inconsistent findings regarding the effects of sleep deprivation on levels of neuroinflammatory markers in the epileptic brain have been reported.…”