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.

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.

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.

scholarly journals Spontaneous and influenza virus-induced sleep are altered in TNF-α double-receptor deficient mice

2008 ◽  
Vol 105 (4) ◽  
pp. 1187-1198 ◽  
Author(s):  
Levente Kapás ◽  
Stewart G. Bohnet ◽  
Tim R. Traynor ◽  
Jeannine A. Majde ◽  
Éva Szentirmai ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Eye Movement ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Sleep Regulation ◽  
Viral Challenge ◽  
Delta Power ◽  
Tnf Α ◽  
Health And Disease ◽  
Factor Α

Tumor necrosis factor-α (TNF-α) is associated with sleep regulation in health and disease. Previous studies assessed sleep in mice genetically deficient in the TNF-α 55-kDa receptor. In this study, spontaneous and influenza virus-induced sleep profiles were assessed in mice deficient in both the 55-kDa and 75-kDa TNF-α receptors [TNF-2R knockouts (KO)] and wild-type (WT) strain controls. Under baseline conditions the TNF-2R KO mice had less non-rapid eye movement sleep (NREMS) than WTs during the nighttime and more rapid eye movement sleep (REMS) than controls during the daytime. The differences between nighttime maximum and daytime minimum values of electroencephalogram (EEG) delta power during NREMS were greater in the TNF-2R KO mice than in WTs. Viral challenge (mouse-adapted influenza X-31) enhanced NREMS and decreased REMS in both strains roughly to the same extent. EEG delta power responses to viral challenge differed substantially between strains; the WT animals increased, whereas the TNF-2R KO mice decreased their EEG delta wave power during NREMS. There were no differences between strains in body temperatures or locomotor activity in uninfected mice or after viral challenge. Analyses of cortical mRNAs confirmed that the TNF-2R KO mice lacked both TNF-α receptors; these mice also had higher levels of orexin mRNA and reduced levels of the purine P2X7 receptor compared with WTs. Results reinforce the hypothesis that TNF-α is involved in physiological sleep regulation but plays a limited role in the acute-phase response induced by influenza virus.

scholarly journals Tumor Necrosis Factor Antagonism Normalizes Rapid Eye Movement Sleep in Alcohol Dependence

2009 ◽  
Vol 66 (2) ◽  
pp. 191-195 ◽  
Author(s):  
Michael R. Irwin ◽  
Richard Olmstead ◽  
Edwin M. Valladares ◽  
Elizabeth Crabb Breen ◽  
Cindy L. Ehlers
Keyword(s):  
Tumor Necrosis Factor ◽  
Alcohol Dependence ◽  
Eye Movement ◽  
Tumor Necrosis ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Necrosis Factor

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.

scholarly journals Sleep/Wake Behavior and EEG Signatures of the TgF344-AD Rat Model at the Prodromal Stage

2020 ◽  
Vol 21 (23) ◽  
pp. 9290
Author(s):  
Matthias Kreuzer ◽  
Glenda L. Keating ◽  
Thomas Fenzl ◽  
Lorenz Härtner ◽  
Christopher G. Sinon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Eye Movement ◽  
Rat Model ◽  
Protein Modification ◽  
Light Cycle ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Dark Light ◽  
Eeg Features

Transgenic modification of the two most common genes (APPsw, PS1ΔE9) related to familial Alzheimer’s disease (AD) in rats has produced a rodent model that develops pathognomonic signs of AD without genetic tau-protein modification. We used 17-month-old AD rats (n = 8) and age-matched controls (AC, n = 7) to evaluate differences in sleep behavior and EEG features during wakefulness (WAKE), non-rapid eye movement sleep (NREM), and rapid eye movement sleep (REM) over 24-h EEG recording (12:12h dark–light cycle). We discovered that AD rats had more sleep–wake transitions and an increased probability of shorter REM and NREM bouts. AD rats also expressed a more uniform distribution of the relative spectral power. Through analysis of information content in the EEG using entropy of difference, AD animals demonstrated less EEG information during WAKE, but more information during NREM. This seems to indicate a limited range of changes in EEG activity that could be caused by an AD-induced change in inhibitory network function as reflected by increased GABAAR-β2 expression but no increase in GAD-67 in AD animals. In conclusion, this transgenic rat model of Alzheimer’s disease demonstrates less obvious EEG features of WAKE during wakefulness and less canonical features of sleep during sleep.

Vagotomy attenuates tumor necrosis factor-α-induced sleep and EEG δ-activity in rats

2001 ◽  
Vol 280 (4) ◽  
pp. R1213-R1220 ◽  
Author(s):  
Takeshi Kubota ◽  
Jidong Fang ◽  
Zhiwei Guan ◽  
Richard A. Brown ◽  
James M. Krueger
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Brain Temperature ◽  
Vagal Afferents ◽  
Sleep Regulation ◽  
Cytokine Network ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Much evidence suggests that tumor necrosis factor-α (TNF-α) is involved in the regulation of physiological sleep. However, it remains unclear whether peripheral administration of TNF-α induces sleep in rats. Furthermore, the role of the vagus nerve in the somnogenic actions of TNF-α had not heretofore been studied. Four doses of TNF-α were administered intraperitoneally just before the onset of the dark period. The three higher doses of TNF-α (50, 100, and 200 μg/kg) dose dependently increased nonrapid eye movement sleep (NREMS), accompanied by increases in electroencephalogram (EEG) slow-wave activity. TNF-α increased EEG δ-power and decreased EEG α- and β-power during the initial 3 h after injection. In vagotomized rats, the NREMS responses to 50 or 100 μg/kg of TNF-α were attenuated, while significant TNF-α-induced increases in NREMS were observed in a sham-operated group. Moreover, the vagotomized rats failed to exhibit the increase in EEG δ-power induced by TNF-α intraperitoneally. These results suggest that peripheral TNF-α can induce NREMS and vagal afferents play an important role in the effects of peripheral TNF-α and EEG synchronization on sleep. Intraperitoneal TNF-α failed to affect brain temperature at the doses tested, thereby demonstrating that TNF-α-induced sleep effects are, in part, independent from its effects on brain temperature. Results are consistent with the hypothesis that a cytokine network is involved in sleep regulation.

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.

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