Brain-specific interleukin-1 receptor accessory protein in sleep regulation (original) (raw)
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American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2004
Interleukin 1β (IL-1) is a key mediator of the acute phase response in an infected host and acts centrally to coordinate responses to an immune challenge, such as fever and increased non-rapid eye movement (NREM) sleep. The preoptic area (POA) is a primary sleep regulatory center in the brain: the ventrolateral POA (VLPO) and median preoptic nucleus (MnPN) each contain high numbers of c-Fos protein immunoreactive (IR) neurons after sleep but not after waking. We hypothesized that IL-1 mediates increased NREM sleep through activation of these sleep-active sites. Rats injected intracerebroventricularly with IL-1 (10 ng) at dark onset spent significantly more time in NREM sleep 4–5 h after injection. This increase in NREM sleep was associated with increased numbers of Fos-IR neurons in the MnPN, but not in the VLPO. Fos IR in the rostral MnPN was significantly increased 2 h post IL-1 injection, although the percentage of NREM sleep in the preceding 2 h was the same as controls. Fos IR ...
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1998
To determine the site of action of the sleep-promoting effect of interleukin-1 (IL-1), we continuously infused (between 11 P.M. and 5 A.M.) murine recombinant IL-1beta into seven different locations in the ventricular and subarachnoid systems of the brain in freely moving rats. When IL-1 was infused at 10 ng/6 hr into the subarachnoid space underlying the ventral surface of the rostral basal forebrain, which previously was defined as the "prostaglandin (PG) D2-sensitive sleep-promoting zone" (PGD2-SZ), the total amount of slow-wave sleep (SWS) increased by 110.7 min (IL-1 was 208.1 +/- 14.3 min vs control at 97.4 +/- 9.3 min; n = 8; p < 0.01 by paired Student's t test) from the baseline control level obtained under continuous infusion of saline vehicle. The hourly SWS during the infusion period reached the level of daytime SWS, the physiological maximum, whereas paradoxical sleep (PS) was decreased transiently. This site of action for the SWS promotion was dissociat...
European Journal of Neuroscience, 2004
Interleukin-1b (IL-1) is a pro-inflammatory cytokine that has been implicated in the regulation of nonrapid eye movement (nonREM) sleep. IL-1, IL-1 receptors and the IL-1 receptor antagonist (ra) are present normally in discrete brain regions, including the preoptic area (POA) of the hypothalamus and the adjoining magnocellular basal forebrain (BF). The POA ⁄ BF have been implicated in the regulation of sleep-wakefulness. We hypothesized that IL-1 promotes nonREM sleep, in part by altering the state-dependent discharge activity of POA ⁄ BF neurons. We recorded the sleep-wake discharge profiles of 83 neurons in the lateral POA ⁄ BF and assessed the effects of IL-1, IL-1ra, and IL-ra + IL-1 delivered through a microdialysis probe on state-dependent neuronal discharge activity. IL-1 decreased the discharge rate of POA ⁄ BF neurons as a group (n = 55) but wake-related and sleep-related neurons responded differently. IL-1 significantly decreased the discharge rate of wake-related neurons. Of 24 wake-related neurons studied, 19 (79%) neurons exhibited a greater than 20% change in their discharge in the presence of IL-1 during waking. IL-1 suppressed the discharge activity of 18 of 19 responsive neurons. Of 13 sleep-related neurons studied, IL-1 increased the discharge activity of five and suppressed the discharge activity of four neurons. IL-1ra increased the discharge activity of four of nine neurons and significantly attenuated IL-1-induced effects on neuronal activity of POA ⁄ BF neurons (n = 19). These results suggest that the sleep-promoting effects of IL-1 may be mediated, in part, via the suppression of wake-related neurons and the activation of a subpopulation of sleeprelated neurons in the POA ⁄ BF.
The relationship of interleukin-1 and immune functions to sleep in humans
Psychosomatic Medicine, 1986
Serial sampling of peripheral blood from six healthy adult male volunteers was performed during daytime waking and nighttime sleeping. In addition, sleep physiology was assessed in all subjects (Ss) and sleep stages scored blind by standard criteria. Samples of plasma were analyzed for cortisol (Co) levels, functional interleukin-1 (IL-1), and interleukin-2 (IL-2) activity. Peripheral blood monocytes (PBM) were assayed to evaluate natural killer (NK) activity and mitogen responsiveness. Dramatic increase in IL-1 activity along with changes in other immune functions occurred during sleep and were related to onset of slow wave sleep.
Brain, behavior, and immunity, 2017
Both sleep loss and pathogens can enhance brain inflammation, sleep, and sleep intensity as indicated by electroencephalogram delta (δ) power. The pro-inflammatory cytokine interleukin-1 beta (IL-1β) is increased in the cortex after sleep deprivation (SD) and in response to the Gram-negative bacterial cell-wall component lipopolysaccharide (LPS), although the exact mechanisms governing these effects are unknown. The nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome protein complex forms in response to changes in the local environment and, in turn, activates caspase-1 to convert IL-1β into its active form. SD enhances the cortical expression of the somnogenic cytokine IL-1β, although the underlying mechanism is, as yet, unidentified. Using NLRP3-gene knockout (KO) mice, we provide evidence that NLRP3 inflammasome activation is a crucial mechanism for the downstream pathway leading to increased IL-1β-enhanced sleep. NLRP3 KO mice exhibited reduced non-ra...
Cytokines in immune function and sleep regulation
Handbook of Clinical Neurology, 2011
There are two somewhat independent literatures concerning the fundamental mechanisms of sleep regulation. One is based on neurophysiological methods; this literature has led to the identification of circuits involved in NREMS regulation such as corticothalamic projections, ventrolateral preoptic (VLPO) and median preoptic (MnPO) circuits. 81,90 Satisfactory explanations of how these circuits impose sleep on the brain and how they keep track of past sleep-wake activity are not yet available. A second sleep regulatory literature is based on biochemical methods. This work has its basis in the homeostatic nature of sleep and the nearly 100-year-old finding, replicated many times, that the transfer of cerebrospinal fluid (CSF) from sleep-deprived, but not control, animals enhances sleep in the recipients. Within the past 20 years several sleep regulatory substances (SRSs) have been identified and extensively tested in that they have met all the criteria for SRSs. 11,48, This literature provides a mechanistic explanation for sleep homeostasis but has only begun to address the issues of the cellular mechanisms leading to sleep. This review discusses SRS that are linked to host-defense; we focus on interlukin-1β (IL1β), tumor necrosis factor α (TNFα) and interferons (IFNs). We also briefly discuss how sleep is part of the acute phase response induced by viral challenge.
Spontaneous, homeostatic, and inflammation-induced sleep in NF- B p50 knockout mice
AJP: Regulatory, Integrative and Comparative Physiology, 2006
The dimeric transcription factor nuclear factor-κB (NF-κB) regulates several endogenous sleep-modulatory substances and thereby serves as a pivotal mediator of sleep-wake homeostasis. To further define the role of NF-κB in sleep regulation, we monitored sleep and temperature in mice that lack the p50 subunit of NF-κB [p50 knockout (KO) mice]. Compared with the control B6129PF2/J strain, p50 KO mice spend more time in slow-wave sleep (SWS) and rapid eye movement sleep (REMS) under normal conditions and show enhanced homeostatic recovery of sleep after sleep loss. p50 KO mice also show increased SWS and reduced REMS and temperature after the administration of lipopolysaccharide, yet they are behaviorally less responsive to challenge with influenza virus. These data support a role for NF-κB, and, in particular, for the p50 subunit, in the regulation of sleep in healthy mice and in mice experiencing immune challenge.
Mediators of Inflammation and Their Interaction with Sleep
Annals of the New York Academy of Sciences, 2006
In humans, activation of the primary host defense system leads to increased or decreased NREM sleep quality, depending on the degree of early immune activation. Modest elevations of certain inflammatory cytokines are found during experimental sleep loss in humans and, in addition, relatively small elevations of cytokines are seen following commencement of pharmacological treatments with clozapine, a CNS active antipsychotic agent, known to have immunomodulatory properties. Cytokines such as TNF-␣, its soluble receptors, and IL-6, present in the periphery and the CNS, comprise a link between peripheral immune stimulation and CNS-mediated behaviors and experiences such as sleep, sleepiness, and fatigue. The debilitating fatigue experienced in chronic fatigue syndrome and related diseases may also be related to altered cytokine profiles.
Interleukin-1 receptor (IL-1R) mediates epilepsy-induced sleep disruption
BMC Neuroscience
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 epilepsyinduced 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.