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.

A cyclooxygenase-2 inhibitor attenuates spontaneous and TNF-α-induced non-rapid eye movement sleep in rabbits

2003 ◽  
Vol 285 (1) ◽  
pp. R99-R109 ◽  
Author(s):  
Hitoshi Yoshida ◽  
Takeshi Kubota ◽  
James M. Krueger
Keyword(s):  
Eye Movement ◽  
Slow Wave ◽  
Brain Temperature ◽  
Wave Activity ◽  
Slow Wave Activity ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Tnf Α ◽  
Cox 2 ◽  
The Brain

Sleep is regulated in part by the brain cytokine network, including tumor necrosis factor-α (TNF-α). TNF-α activates the transcription factor nuclear factor-κB, which in turn promotes transcription of many genes, including cyclooxygenase-2 (COX-2). COX-2 is in the brain and is an enzyme responsible for production of prostaglandin D2. The hypothesis that central COX-2 plays a role in the regulation of spontaneous and TNF-α-induced sleep was investigated. Three doses (0.5, 5, and 50 μg) of NS-398, a highly selective COX-2 inhibitor, were injected intracerebroventricularly. The highest dose decreased non-rapid eye movement sleep. The intermediate and highest doses decreased electroencephalographic slow-wave activity; the greatest reduction occurred after 50 μg of NS-398 during the first 3-h postinjection period. Rapid eye movement sleep and brain temperature were not altered by any dose of NS-398. Pretreatment of rabbits with 5 or 50 μg of NS-398 blocked the TNF-α-induced increases in non-rapid eye movement sleep, electroencephalographic slow-wave activity, and brain temperature. These data suggest that COX-2 is involved in the regulation of spontaneous and TNF-α-induced sleep.

Influenza virus-induced sleep responses in mice with targeted disruptions in neuronal or inducible nitric oxide synthases

2004 ◽  
Vol 97 (1) ◽  
pp. 17-28 ◽  
Author(s):  
Lichao Chen ◽  
Deborah Duricka ◽  
Scott Nelson ◽  
Sanjib Mukherjee ◽  
Stewart G. Bohnet ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Eye Movement ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
No Synthase ◽  
Cytokine Gene Expression ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
The Brain

Influenza viral infection induces increases in non-rapid eye movement sleep and decreases in rapid eye movement sleep in normal mice. An array of cytokines is produced during the infection, and some of them, such as IL-1β and TNF-α, are well-defined somnogenic substances. It is suggested that nitric oxide (NO) may mediate the sleep-promoting effects of these cytokines. In this study, we use mice with targeted disruptions of either the neuronal NO synthase (nNOS) or the inducible NO synthase (iNOS) gene, commonly referred to as nNOS or iNOS knockouts (KOs), to investigate sleep changes after influenza viral challenge. We report that the magnitude of viral-induced non-rapid eye movement sleep responses in both nNOS KOs and iNOS KOs was less than that of their respective controls. In addition, the duration of rapid eye movement sleep in nNOS KO mice did not decrease compared with baseline values. All strains of mice had similar viral titers and cytokine gene expression profiles in the lungs. Virus was not isolated from the brains of any strain. However, gene expression in the brain stem differed between nNOS KOs and their controls: mRNA for the interferon-induced gene 2′,5′-oligoadenylate synthase 1a was elevated in nNOS KOs relative to their controls at 15 h, and IL-1β mRNA was elevated in nNOS KOs relative to their controls at 48 h. Our results suggest that NO synthesized by both nNOS and iNOS plays a role in virus-induced sleep changes and that nNOS may modulate cytokine expression in the brain.

Inhibition of nitric oxide synthesis suppresses sleep in rabbits

1994 ◽  
Vol 266 (1) ◽  
pp. R151-R157 ◽  
Author(s):  
L. Kapas ◽  
M. Shibata ◽  
M. Kimura ◽  
J. M. Krueger
Keyword(s):  
Nitric Oxide ◽  
Eye Movement ◽  
Brain Temperature ◽  
Interleukin 1 ◽  
Systemic Blood Pressure ◽  
Common Mechanism ◽  
Rapid Eye Movement ◽  
Nitric Oxide Synthesis ◽  
Rapid Eye Movement Sleep ◽  
Intracerebroventricular Injections

The effects of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis, on spontaneous and interleukin-1 (IL-1)-induced sleep were examined in rabbits. Animals were injected intracerebroventricularly or intravenously during the light phase with vehicle, L-NAME, IL-1, or the combination of L-NAME and IL-1. Injection of L-NAME (5 mg icv and 100 mg/kg iv) suppressed both non-rapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) for 4-6 h. The sleep-suppressive effects are unlikely due to pressor responses to L-NAME because administration of L-NAME (5 mg icv) produced only a transient (3-4 min) slight increase in systemic blood pressure. Injection of IL-1 (20 ng icv) elicited fever, suppressed REMS, and increased NREMS for 6 h. NREMS was suppressed for 3 h after the combined intracerebroventricular injections of 5 mg L-NAME and 20 ng IL-1 and was elevated during postinjection hours 4-6. Administration of IL-1 (30 ng/kg iv) increased NREMS and brain temperature for 2 h. After the combined injection of IL-1 and L-NAME (100 mg/kg), NREMS was significantly suppressed during postinjection hours 1-5. It is not known whether the interactions between the sleep-suppressive effects of L-NAME and the NREMS-promoting effects of IL-1 are specific, being mediated via a common mechanism, or whether they are additive, being mediated via independent mechanisms. The pyrogenic and REMS-suppressive actions of either intracerebroventricularly or intravenously injected IL-1 were not affected by L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)

Pregnancy-associated sleep changes in the rat

1996 ◽  
Vol 271 (4) ◽  
pp. R1063-R1069 ◽  
Author(s):  
M. Kimura ◽  
S. Q. Zhang ◽  
S. Inoue
Keyword(s):  
Sleep Disorder ◽  
Eye Movement ◽  
Brain Temperature ◽  
Early Period ◽  
Underlying Mechanism ◽  
Normal Pregnancy ◽  
Female Rats ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Before And After

Sleep disorder during the course of pregnancy has been recently recognized in humans. However, the underlying mechanism of pregnancy-associated sleep disorder remains undetermined, and sleep changes even during normal pregnancy have not been fully understood. To describe the effects of pregnancy on sleep, sleep-wake patterns before and after fertile mating were compared in an animal model. Baseline recordings of sleep and brain temperature were made throughout a normal 4-day estrous cycle in female rats. After the rats became pregnant, the recordings continued across the entire pregnant period. Compared with baseline sleep before mating, both non-rapid eye movement sleep and rapid eye movement sleep increased significantly from the first night of pregnancy. Although rapid eye movement sleep returned to the baseline level from midpregnancy, nocturnal non-rapid eye movement sleep stayed enhanced during the entire pregnant period. Daytime sleep fluctuated toward the end of pregnancy. Brain temperature was elevated during the early period of pregnancy but did not correlate with enhanced sleep. The results suggest that physiological changes in different stages of pregnancy may contribute to the regulation of maternal sleep and temperature.

Effect of elevated ambient temperature on sleep, EEG spectra, and brain temperature in the rat

1995 ◽  
Vol 268 (6) ◽  
pp. R1365-R1373 ◽  
Author(s):  
B. O. Gao ◽  
P. Franken ◽  
I. Tobler ◽  
A. A. Borbely
Keyword(s):  
Ambient Temperature ◽  
Eye Movement ◽  
Spectral Power ◽  
Dark Period ◽  
Brain Temperature ◽  
Spectral Power Density ◽  
State Transitions ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Hypothalamic Temperature

To examine the relationship between sleep and brain temperature in the rat, the vigilance states, spectral power density of the electroencephalogram (EEG), hypothalamic temperature (T(hy)), and cortical temperature (Tcr) were recorded for 3 days. A 1-day rise of ambient temperature from 23 to 30 degrees C did not affect the percentage of waking, non-rapid eye movement sleep (NREMS), and rapid eye movement sleep (REMS), but increased EEG slow-wave activity in NREMS in the 12-h dark period. T(hy) was invariably higher than Tcr, but at 30 degrees C the difference diminished because of a rise in Tcr. In contrast to Tcr, T(hy) was only slightly increased at 30 degrees C and only during sleep and in the dark period. Although the temperatures changed largely in parallel at vigilance state transitions, Tcr rose more rapidly than T(hy) at NREMS-REMS transitions and more slowly at NREMS-waking transitions. T(hy) declined more rapidly than Tcr at waking-NREMS transitions and more slowly at REMS-NREMS transitions. The results are consistent with a central role of the hypothalamus in the activation and deactivation of the waking state.

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.

Startle-evoked changes in diaphragmatic activity during wakefulness and sleep

1990 ◽  
Vol 68 (1) ◽  
pp. 166-173 ◽  
Author(s):  
L. R. Kline ◽  
J. C. Hendricks ◽  
D. A. Silage ◽  
A. R. Morrison ◽  
R. O. Davies ◽  
...  
Keyword(s):  
Eye Movement ◽  
Startle Response ◽  
Moving Average ◽  
Respiratory Muscles ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Neural Basis ◽  
Excitatory Response ◽  
Muscle Atonia ◽  
The Brain

Tonic inhibition of some respiratory muscles occurs as part of the generalized muscle atonia of rapid-eye-movement sleep (REMS). A second type of inhibition of the diaphragm during REMS, fractionations, consists of brief pauses in the diaphragmatic electromyogram (DIA EMG) in association with phasic events. Because motor inhibition can occur as part of the startle response, and the brain is highly activated during REMS, we hypothesized that the neural basis of the fractionations might be activation of a startle network. To test this hypothesis, tone bursts (100 dB, 20-ms duration at 15-s intervals) were applied to cats at a fixed inspiratory level in the DIA moving average during REMS, non-rapid-eye-movement sleep (NREMS), and wakefulness. Parallel sham studies (no tone applied) were obtained for each state. The response of the DIA EMG was averaged over 100 ms by using the tone pulse as a trigger, and the following parameters of the DIA EMG were measured: latency to peak and/or nadir, increment or decrement in activity, and duration of peak and/or nadir. After a tone, all five animals studied displayed a profound suppression of DIA activity during REMS (latency to nadir 42.4 +/- 10.0 ms, duration of suppression 35.9 +/- 17.6 ms). Similarly, DIA activity was suppressed in all cats during NREMS (latency to nadir 40.9 +/- 13.3 ms, duration 23.9 +/- 13.4 ms). An excitatory response was observed in only two cats during NREMS and wakefulness. The similarity of startle-induced DIA EMG pauses to spontaneous fractionations of DIA activity during REMS suggests that the latter result from activation of a central startle system.

scholarly journals Sleep spindles are resilient to extensive white matter deterioration

2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Erlan Sanchez ◽  
Caroline Arbour ◽  
Héjar El-Khatib ◽  
Karine Marcotte ◽  
Hélène Blais ◽  
...  
Keyword(s):  
White Matter ◽  
Eye Movement ◽  
Control Group ◽  
Sleep Spindles ◽  
Rapid Eye Movement ◽  
Sleep Spindle ◽  
Rapid Eye Movement Sleep ◽  
Brain Injured ◽  
Healthy Control ◽  
The Brain

Abstract Sleep spindles are an essential part of non-rapid eye movement sleep, notably involved in sleep consolidation, cognition, learning and memory. These oscillatory waves depend on an interaction loop between the thalamus and the cortex, which relies on a structural backbone of thalamo-cortical white matter tracts. It is still largely unknown if the brain can properly produce sleep spindles when it underwent extensive white matter deterioration in these tracts, and we hypothesized that it would affect sleep spindle generation and morphology. We tested this hypothesis with chronic moderate to severe traumatic brain injury (n = 23; 30.5 ± 11.1 years old; 17 m/6f), a unique human model of extensive white matter deterioration, and a healthy control group (n = 27; 30.3 ± 13.4 years old; 21m/6f). Sleep spindles were analysed on a full night of polysomnography over the frontal, central and parietal brain regions, and we measured their density, morphology and sigma-band power. White matter deterioration was quantified using diffusion-weighted MRI, with which we performed both whole-brain voxel-wise analysis (Tract-Based Spatial Statistics) and probabilistic tractography (with High Angular Resolution Diffusion Imaging) to target the thalamo-cortical tracts. Group differences were assessed for all variables and correlations were performed separately in each group, corrected for age and multiple comparisons. Surprisingly, although extensive white matter damage across the brain including all thalamo-cortical tracts was evident in the brain-injured group, sleep spindles remained completely undisrupted when compared to a healthy control group. In addition, almost all sleep spindle characteristics were not associated with the degree of white matter deterioration in the brain-injured group, except that more white matter deterioration correlated with lower spindle frequency over the frontal regions. This study highlights the resilience of sleep spindles to the deterioration of all white matter tracts critical to their existence, as they conserve normal density during non-rapid eye movement sleep with mostly unaltered morphology. We show that even with such a severe traumatic event, the brain has the ability to adapt or to withstand alterations in order to conserve normal sleep spindles.

Proton pump inhibitors associated with rapid eye movement sleep behaviour disorder

2021 ◽  
Vol 14 (12) ◽  
pp. e246469
Author(s):  
Ruwanthi Jayasekara ◽  
Ian Smith
Keyword(s):  
Eye Movement ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Acid Reflux ◽  
High Dose ◽  
Rapid Eye Movement ◽  
Rapid Eye Movement Sleep ◽  
Behaviour Disorder ◽  
Sleep Behaviour ◽  
The Central Nervous System

We present the case of a 65-year-old woman diagnosed with rapid eye movement sleep behaviour disorder (REMBD) based on typical symptoms and confirmed with an inpatient polysomnogram. She was prescribed clonazepam and later temazepam but continued to have intrusive symptoms. She subsequently recalled that the onset of dream enactment coincided with starting high-dose omeprazole for acid reflux. With this insight, she stopped the omeprazole. Within days, the dream enactment and nocturnal movements subsided. She stopped taking the temazepam and was symptom free for a few months. However, she was started on lansoprazole for recurrent dyspepsia. Once again she experienced violent movements in sleep. This is the first time an association between proton pump inhibitors (PPIs) and REMBD has been reported. PPIs have many effects on the central nervous system and should be considered as a possible provoking factor in people presenting with REMBD.

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