Nuclear factor-κB inhibitor peptide inhibits spontaneous and interleukin-1β-induced sleep

2000 ◽  
Vol 279 (2) ◽  
pp. R404-R413 ◽  
Author(s):  
Takeshi Kubota ◽  
Tetsuya Kushikata ◽  
Jidong Fang ◽  
James M. Krueger
Keyword(s):  
Eye Movement ◽  
Nuclear Factor Κb ◽  
Current Data ◽  
Interleukin 1Β ◽  
Nuclear Factor ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Sleep Regulation ◽  
Cytokine Network ◽  
Inhibitor Peptide

Nuclear factor-κB (NF-κB) is a transcription factor that when activated promotes production of several sleep-promoting substances such as interleukin-1β (IL-1β), tumor necrosis factor-α, and nerve growth factor. Therefore, we hypothesized that inhibition of NF-κB activation would attenuate sleep. A NF-κB cell-permeable inhibitor peptide (IP) was injected intracerebroventricularly (5 and 50 μg for rats, 100 μg for rabbits). On a separate day, time-matched control injections of a cell-permeable inactive control peptide were done in the same animals. The 50-μg dose of IP in rats and the 100-μg dose in rabbits significantly inhibited non-rapid eye movement sleep and rapid eye movement sleep if administered during the light period. Moreover, pretreatment of rabbits with 100 μg of the IP 12 h before intracerebroventricular injection of IL-1β (10 ng) significantly attenuated IL-1β-induced sleep and febrile responses. The current data support the hypothesis that a brain cytokine network is involved in sleep regulation and that NF-κB is a crucial factor in physiological sleep regulation.

Interleukin-4 inhibits spontaneous sleep in rabbits

1998 ◽  
Vol 275 (4) ◽  
pp. R1185-R1191 ◽  
Author(s):  
Tetsuya Kushikata ◽  
Jidong Fang ◽  
Ying Wang ◽  
James M. Krueger
Keyword(s):  
Eye Movement ◽  
Interleukin 4 ◽  
Light Cycle ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Sleep Regulation ◽  
Cytokine Network ◽  
Factor Α ◽  
Physiological Sleep ◽  
Necrosis Factor

Proinflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α, are involved in sleep regulation. IL-4 is an antiinflammatory cytokine that inhibits proinflammatory cytokine production. The hypothesis that IL-4 should attenuate sleep was studied by determining the effects of IL-4 on rabbit spontaneous sleep. Thirty-six rabbits were used. Four doses of IL-4 (0.25, 2.5, 25, and 250 ng) were injected intracerebroventricularly during the rest (light) period. One dose of IL-4 (25 ng) was injected during the active (dark) cycle. Appropriate time-matched control injections of saline were done in the same rabbits on different days. The three highest doses of IL-4 significantly inhibited spontaneous non-rapid eye movement sleep if IL-4 was given during the light cycle. The highest dose of IL-4 (250 ng) also significantly decreased rapid eye movement sleep. On the other hand, IL-4 administered at dark onset had no effect on sleep. The sleep inhibitory properties of IL-4 provide additional evidence for the hypothesis that a brain cytokine network is involved in the regulation of physiological sleep.

Interleukin-15 and interleukin-2 enhance non-REM sleep in rabbits

2001 ◽  
Vol 281 (3) ◽  
pp. R1004-R1012 ◽  
Author(s):  
Takeshi Kubota ◽  
Richard A. Brown ◽  
Jidong Fang ◽  
James M. Krueger
Keyword(s):  
Eye Movement ◽  
Interleukin 2 ◽  
Signal Transduction Pathway ◽  
Current Data ◽  
Light Period ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Cytokine Network ◽  
Interleukin 15 ◽  
The Brain

Interleukin (IL)-15 and -2 share receptor- and signal-transduction pathway (Jak-STAT pathway) components. IL-2 is somnogenic in rats but has not been tested in other species. Furthermore, the effects of IL-15 on sleep have not heretofore been described. We investigated the somnogenic actions of IL-15 in rabbits and compared them with those of IL-2. Three doses of IL-15 or -2 (10, 100, and 500 ng) were injected intracerebroventriculary at the onset of the dark period. In addition, 500 ng of IL-15 and -2 were injected 3 h after the beginning of the light period. IL-15 dose dependently increased non-rapid eye movement sleep (NREMS) and induced fever. IL-15 inhibited rapid eye movement sleep (REMS) after its administration during the light period; however, all doses of IL-15 failed to affect REMS if given at dark onset. IL-2 also dose dependently increased NREMS and fever. IL-2 inhibited REMS, and this effect was observed only in the light period. IL-15 and -2 enhanced electroencephalographic (EEG) slow waves during the initial 9-h postinjection period, then, during hours 10–23postinjection, reduced EEG slow-wave activity. Current data support the notion that the brain cytokine network is involved in the regulation of sleep.

Effects of interleukin-1β on sleep are mediated by the type I receptor

1998 ◽  
Vol 274 (3) ◽  
pp. R655-R660 ◽  
Author(s):  
Jidong Fang ◽  
Ying Wang ◽  
James M. Krueger
Keyword(s):  
Eye Movement ◽  
Dark Period ◽  
Interleukin 1Β ◽  
Type I ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Sleep Regulation ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Interleukin-1β (IL-1β) is a well characterized sleep regulatory substance. To study receptor mechanisms for the sleep-promoting effects of IL-1β, sleep patterns were determined in control and IL-1 type I receptor knockout (IL-1RI KO) mice with a B6x129 background after intraperitoneal injections of saline or murine recombinant IL-1β. The IL-1RI KO mice had slightly but significantly less sleep during the dark period compared with the controls. IL-1β dose dependently increased non-rapid eye movement sleep (NREMS) and suppressed rapid eye movement sleep (REMS) in the controls. The IL-1RI KO mice did not respond to IL-1β. In contrast, the IL-1RI KO mice increased NREMS and decreased REMS after administration of tumor necrosis factor-α (TNF-α), another well characterized sleep-promoting substance. These results 1) provide further evidence that IL-1β is involved in sleep regulation, 2) indicate that the effects of IL-1β on sleep are mediated by the type I receptor, and 3) suggest that TNF-α is capable of inducing sleep without the involvement of IL-1.

Epidermal growth factor enhances spontaneous sleep in rabbits

1998 ◽  
Vol 275 (2) ◽  
pp. R509-R514 ◽  
Author(s):  
Tetsuya Kushikata ◽  
Jidong Fang ◽  
Zutang Chen ◽  
Ying Wang ◽  
James M. Krueger
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Eye Movement ◽  
Brain Temperature ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Sleep Regulation ◽  
Guide Cannula ◽  
Epidermal Growth

Several growth factors are implicated in sleep regulation. Epidermal growth factor (EGF) is found in the brain, and it influences the production of several sleep-promoting substances. We determined, therefore, whether administration of exogenous EGF affected spontaneous sleep in rabbits. Twenty-five rabbits were implanted with electroencephalographic electrodes, a brain thermistor, and an intracerebroventricular guide cannula. Three doses of EGF (0.5, 5, and 25 μg) were used. The animals were injected intracerebroventricularly with saline as control and one dose of EGF on 2 separate days. Five and twenty-five micrograms of EGF enhanced non-rapid eye movement sleep and increased brain temperature. The 25-μg dose of EGF also inhibited rapid eye movement sleep across the 23-h postinjection recording period. Results are consistent with the hypothesis that EGF, like other growth factors, could be involved in sleep regulation.

Varying photoperiod in the laboratory rat: profound effect on 24-h sleep pattern but no effect on sleep homeostasis

1995 ◽  
Vol 269 (3) ◽  
pp. R691-R701 ◽  
Author(s):  
P. Franken ◽  
I. Tobler ◽  
A. A. Borbely
Keyword(s):  
Eye Movement ◽  
Slow Wave ◽  
Wave Activity ◽  
Slow Wave Activity ◽  
Sleep Pattern ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Sleep Regulation ◽  
Marked Rise ◽  
Laboratory Rats

To assess the influence of the photoperiod on sleep regulation, laboratory rats were adapted to a long photoperiod (LPP; 16:8-h light-dark cycle, LD 16:8) or a short photoperiod (SPP; LD 8:16). The electroencephalogram (EEG) and cortical temperature (TCRT) were continuously recorded for a baseline day, a 24-h sleep deprivation (SD) period, and a recovery day. Data obtained previously for LD 12:12 served for comparison. Whereas the photoperiod exerted a prominent effect on the 24-h sleep pattern, the 24-h baseline level of sleep and the response to SD were little affected. Recovery from SD was characterized by a marked rise in rapid eye movement sleep, a moderate rise in non-rapid eye movement sleep, and an initial enhancement of EEG slow-wave activity followed by a decrease below baseline. The amplitude and phase of the "unmasked" 24-h component of TCRT did not differ between LPP and SPP. Computer simulations demonstrated that the changes of TCRT and EEG slow-wave activity can be largely accounted for by the sequence of the vigilance states. We conclude that the photoperiod does not affect the basic processes underlying sleep regulation.

Subdiaphragmatic vagotomy blocks the sleepand fever-promoting effects of interleukin-1β

1997 ◽  
Vol 273 (4) ◽  
pp. R1246-R1253 ◽  
Author(s):  
Michael K. Hansen ◽  
James M. Krueger
Keyword(s):  
Eye Movement ◽  
Brain Temperature ◽  
Alternative Pathway ◽  
Intraperitoneal Administration ◽  
Vagal Afferents ◽  
Interleukin 1Β ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
The Central Nervous System ◽  
The Brain

The mechanism by which peripheral cytokines signal the central nervous system to elicit central manifestations of the acute phase response remains unknown. Recent evidence suggests that cytokines may signal the brain via the vagus nerve. To test this possibility, we examined sleep-wake activity and brain temperature (Tbr) after the intraperitoneal administration of saline or three doses (0.1, 0.5, and 2.5 μg/kg) of interleukin-1β (IL-1β) in subdiaphragmatically vagotomized (Vx) and sham-operated (Sham) rats. The lowest dose of IL-1β (0.1 μg/kg) increased non-rapid eye movement sleep (NREMS) and slightly elevated Tbr in Sham rats; both responses were blocked in Vx animals. The middle dose tested (0.5 μg/kg) increased NREMS and Tbr in Sham animals; however, in Vx rats, the increase in NREMS was attenuated and the increase in Tbr was blocked. The highest dose of IL-1β used (2.5 μg/kg) induced increases in NREMS, decreases in rapid eye movement sleep, and a hypothermic response followed by a biphasic fever; these responses were similar in both Sham and Vx rats. These data provide strong evidence that the subdiaphragmatic vagus plays an important role in communicating both sleep and fever signals to the brain. However, there is clearly an alternative pathway by which IL-1 can signal the brain; whether it occurs through activation of other vagal afferents or through direct or indirect actions on the brain remains unknown.

Growth hormone-releasing hormone: cerebral cortical sleep-related EEG actions and expression

2007 ◽  
Vol 293 (2) ◽  
pp. R922-R930 ◽  
Author(s):  
Éva Szentirmai ◽  
Tadanobu Yasuda ◽  
Ping Taishi ◽  
Mingxiang Wang ◽  
Lynn Churchill ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Eye Movement ◽  
Wave Power ◽  
Growth Hormone Releasing Hormone ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Sleep Regulation ◽  
Delta Wave ◽  
Releasing Hormone ◽  
Delta Power

Growth hormone-releasing hormone (GHRH), its receptor (GHRHR), and other members of the somatotropic axis are involved in non-rapid eye movement sleep (NREMS) regulation. Previously, studies established the involvement of hypothalamic GHRHergic mechanisms in NREMS regulation, but cerebral cortical GHRH mechanisms in sleep regulation remained uninvestigated. Here, we show that unilateral application of low doses of GHRH to the surface of the rat somatosensory cortex ipsilaterally decreased EEG delta wave power, while higher doses enhanced delta power. These actions of GHRH on EEG delta wave power occurred during NREMS but not during rapid eye movement sleep. Further, the cortical forms of GHRH and GHRHR were identical to those found in the hypothalamus and pituitary, respectively. Cortical GHRHR mRNA and protein levels did not vary across the day-night cycle, whereas cortical GHRH mRNA increased with sleep deprivation. These results suggest that cortical GHRH and GHRHR have a role in the regulation of localized EEG delta power that is state dependent, as well as in their more classic hypothalamic role in NREMS regulation.

Vasopressin regulates human sleep by reducing rapid-eye-movement sleep

1992 ◽  
Vol 262 (3) ◽  
pp. E295-E300 ◽  
Author(s):  
J. Born ◽  
C. Kellner ◽  
D. Uthgenannt ◽  
W. Kern ◽  
H. L. Fehm
Keyword(s):  
Eye Movement ◽  
Rem Sleep ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Sleep Regulation ◽  
Double Blind ◽  
Physiological Conditions ◽  
Upper Limit ◽  
Stage 2 Sleep ◽  
Time Awake

In two double-blind experiments, effects of intravenous infusion of arginine vasopressin (AVP) on sleep were evaluated in 2 groups of 10 men (20-35 yr). In experiment I, subjects were tested on two occasions, during which they received either placebo or 0.33 IU/h AVP. In experiment II, on three different occasions, subjects received either placebo or 0.66 or 0.99 IU/h AVP. Infusions were administered between 2200 and 0700 h. Nocturnal plasma AVP concentrations were close to the upper limit of the normal physiological range during 0.66 IU/h AVP (16.6 +/- 2.2 pg/ml) but markedly exceeded this range during 0.99 IU/h AVP (25.0 +/- 1.6 pg/ml). Results indicate primary effects of AVP on rapid-eye-movement (REM) sleep, with moderate reductions in REM sleep during 0.33 IU/h AVP (averaging -10.5%) and with substantial reductions in REM sleep (-24.0%) during 0.66 IU/h AVP. During 0.99 IU/h AVP the effect did not further increase (-24.4%). Less consistent effects of AVP were an increase in stage 2 sleep and in time awake. Effects of AVP were not mediated by changes in cortisol or blood pressure. Results suggest AVP to participate in REM sleep regulation under normal physiological conditions.

scholarly journals MicroRNA 132 alters sleep and varies with time in brain

2011 ◽  
Vol 111 (3) ◽  
pp. 665-672 ◽  
Author(s):  
Christopher J. Davis ◽  
James M. Clinton ◽  
Ping Taishi ◽  
Stewart G. Bohnet ◽  
Kimberly A. Honn ◽  
...  
Keyword(s):  
Sleep Deprivation ◽  
Eye Movement ◽  
Dark Period ◽  
Wave Activity ◽  
Light Period ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Direct Effects ◽  
Sleep Regulation ◽  
Light Phase

MicroRNA (miRNA) levels in brain are altered by sleep deprivation; however, the direct effects of any miRNA on sleep have not heretofore been described. We report herein that intracerebroventricular application of a miRNA-132 mimetic (preMIR-132) decreased duration of non-rapid-eye-movement sleep (NREMS) while simultaneously increasing duration of rapid eye movement sleep (REMS) during the light phase. Further, preMIR-132 decreased electroencephalographic (EEG) slow-wave activity (SWA) during NREMS, an index of sleep intensity. In separate experiments unilateral supracortical application of preMIR-132 ipsilaterally decreased EEG SWA during NREMS but did not alter global sleep duration. In addition, after ventricular or supracortical injections of preMIR-132, the mimetic-induced effects were state specific, occurring only during NREMS. After local supracortical injections of the mimetic, cortical miRNA-132 levels were higher at the time sleep-related EEG effects were manifest. We also report that spontaneous cortical levels of miRNA-132 were lower at the end of the sleep-dominant light period compared with at the end of the dark period in rats. Results suggest that miRNAs play a regulatory role in sleep and provide a new tool for investigating sleep regulation.

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