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

View Article: PubMed Central - PubMed

ABSTRACT

Background: 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.

Results: 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.

Conclusions: These results indicate that the IL-1 signal mediates epilepsy-induced sleep disturbance, but dose not participate in kindling-induced epileptogenesis.

No MeSH data available.


Related in: MedlinePlus

The effects of ZT13 kindling stimuli on sleep alterations in wildtype mice. a ZT13 kindling stimuli enhanced NREM sleep during ZT13-18 in the 1st-day after seizure induction, but there was no change on the following day. b ZT13 kindling stimulation did not alter REM sleep. Shadow areas represents the data obtained from baseline control, closed circles represent the data acquired from the 1st-day after seizure induction, and the open circles represents the 2nd-day after seizure induction. c The summary of NREM sleep alteration after ZT13 kindling stimuli. The grey bar represents the data obtained from control, the black bar represents the data acquired from the 1st-day after seizure induction, and the white bar represents the data obtained from the 2nd-day after seizure induction. Asterisk refers to a statistically significant difference between control and the 1st-day after seizure induction. Sleep-wake activity was recorded from the beginning of the dark period (ZT13) and lasted for 24 h
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Fig3: The effects of ZT13 kindling stimuli on sleep alterations in wildtype mice. a ZT13 kindling stimuli enhanced NREM sleep during ZT13-18 in the 1st-day after seizure induction, but there was no change on the following day. b ZT13 kindling stimulation did not alter REM sleep. Shadow areas represents the data obtained from baseline control, closed circles represent the data acquired from the 1st-day after seizure induction, and the open circles represents the 2nd-day after seizure induction. c The summary of NREM sleep alteration after ZT13 kindling stimuli. The grey bar represents the data obtained from control, the black bar represents the data acquired from the 1st-day after seizure induction, and the white bar represents the data obtained from the 2nd-day after seizure induction. Asterisk refers to a statistically significant difference between control and the 1st-day after seizure induction. Sleep-wake activity was recorded from the beginning of the dark period (ZT13) and lasted for 24 h

Mentions: ZT13 kindling stimulation significantly enhanced NREM sleep during ZT13-18 on the 1st-day after seizure induction in IL-1R1 +/+ mice (Fig. 3a). The amount of NREM sleep during ZT13-18 was increased from 11.7 ± 2.3 (obtained before receiving the ZT13 kindling stimulation, the baseline control) to 20.1 ± 2.6% (n = 8) on the 1st-day after seizure induction (p < 0.05 vs. baseline control), and returned to 13.5 ± 2.4% on the 2nd-day after seizure induction (p > 0.05 vs. baseline control; Fig. 3a, c). The difference of NREM sleep acquired before and after kindling stimulation is 8.6 ± 2.5%. ZT13 kindling stimulation did not alter REM sleep during both dark and light periods on the 1st- and 2nd-day after seizure induction (Fig. 3b).Fig. 3


Interleukin-1 receptor (IL-1R) mediates epilepsy-induced sleep disruption
The effects of ZT13 kindling stimuli on sleep alterations in wildtype mice. a ZT13 kindling stimuli enhanced NREM sleep during ZT13-18 in the 1st-day after seizure induction, but there was no change on the following day. b ZT13 kindling stimulation did not alter REM sleep. Shadow areas represents the data obtained from baseline control, closed circles represent the data acquired from the 1st-day after seizure induction, and the open circles represents the 2nd-day after seizure induction. c The summary of NREM sleep alteration after ZT13 kindling stimuli. The grey bar represents the data obtained from control, the black bar represents the data acquired from the 1st-day after seizure induction, and the white bar represents the data obtained from the 2nd-day after seizure induction. Asterisk refers to a statistically significant difference between control and the 1st-day after seizure induction. Sleep-wake activity was recorded from the beginning of the dark period (ZT13) and lasted for 24 h
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5120515&req=5

Fig3: The effects of ZT13 kindling stimuli on sleep alterations in wildtype mice. a ZT13 kindling stimuli enhanced NREM sleep during ZT13-18 in the 1st-day after seizure induction, but there was no change on the following day. b ZT13 kindling stimulation did not alter REM sleep. Shadow areas represents the data obtained from baseline control, closed circles represent the data acquired from the 1st-day after seizure induction, and the open circles represents the 2nd-day after seizure induction. c The summary of NREM sleep alteration after ZT13 kindling stimuli. The grey bar represents the data obtained from control, the black bar represents the data acquired from the 1st-day after seizure induction, and the white bar represents the data obtained from the 2nd-day after seizure induction. Asterisk refers to a statistically significant difference between control and the 1st-day after seizure induction. Sleep-wake activity was recorded from the beginning of the dark period (ZT13) and lasted for 24 h
Mentions: ZT13 kindling stimulation significantly enhanced NREM sleep during ZT13-18 on the 1st-day after seizure induction in IL-1R1 +/+ mice (Fig. 3a). The amount of NREM sleep during ZT13-18 was increased from 11.7 ± 2.3 (obtained before receiving the ZT13 kindling stimulation, the baseline control) to 20.1 ± 2.6% (n = 8) on the 1st-day after seizure induction (p < 0.05 vs. baseline control), and returned to 13.5 ± 2.4% on the 2nd-day after seizure induction (p > 0.05 vs. baseline control; Fig. 3a, c). The difference of NREM sleep acquired before and after kindling stimulation is 8.6 ± 2.5%. ZT13 kindling stimulation did not alter REM sleep during both dark and light periods on the 1st- and 2nd-day after seizure induction (Fig. 3b).Fig. 3

View Article: PubMed Central - PubMed

ABSTRACT

Background: 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 &minus;/&minus; KO) mice.

Results: Our results elucidated the decrease of non-rapid eye movement (NREM) sleep during the light period in IL-1R &minus;/&minus; 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 &minus;/&minus; 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&nbsp;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 &minus;/&minus; KO mice.

Conclusions: These results indicate that the IL-1 signal mediates epilepsy-induced sleep disturbance, but dose not participate in kindling-induced epileptogenesis.

No MeSH data available.


Related in: MedlinePlus