Sleep loss-induced oncogenic pathways are mediated via the neuron-specific interleukin-1 receptor accessory protein (AcPb).

Interleukin-1β (IL1), a pleiotropic cytokine, is involved in sleep regulation, tumor ontogeny, and immune responses. IL1 receptor adaptor proteins, including the IL1 receptor accessory protein (AcP), and its neuron-specific isoform, AcPb, are required for IL1 signaling. The AcPb isoform is resultant from alternate splicing of the AcP transcript.

Tripping on the edge of consciousness.

Herein the major accomplishments, trials and tribulations, and epiphanies experienced by James M. Krueger over the course of his career in sleep research are presented. They include the characterization of a) the supranormal EEG delta waves occurring during NREMS post sleep loss, b) Factor S as a muramyl peptide, c) the physiological roles of cytokines in sleep regulation, d) multiple other sleep regulatory substances, e) the dramatic changes in sleep over the course of infectious diseases, and f) sleep initiation within small neuronal/glial networks.

Night shift schedule alters endogenous regulation of circulating cytokines.

Night shift work is a risk factor for viral infection, suggesting that night shift schedules compromise host defense mechanisms. Prior studies have investigated changes in the temporal profiles of circulating cytokines important for priming and restraining the immune response to infectious challenges from night shift work, but not by way of a 24-h constant routine of continuous wakefulness devoid of behavioral or environmental influences. Hence the true pattern of cytokines, and the combined effect of sleep loss and circadian misalignment on these cytokines remains unknown.

A wake-like state in vitro induced by transmembrane TNF/soluble TNF receptor reverse signaling.

Tumor necrosis factor alpha (TNF) has sleep regulatory and brain development roles. TNF promotes sleep in vivo and in vitro while TNF inhibition diminishes sleep. Transmembrane (tm) TNF and the tmTNF receptors (Rs), are cleaved by tumor necrosis factor alpha convertase to produce soluble (s) TNF and sTNFRs.

Sleep and circadian rhythms: Evolutionary entanglement and local regulation.

Circadian rhythms evolved within single cell organisms and serve to regulate rest-activity cycles in most single-cell and multiple-cell organisms. In contrast, sleep is a network emergent property found in animals with a nervous system. Rhythms and sleep are much entangled involving shared regulatory molecules such as adenosine, ATP, cytokines, neurotrophins, and nitric oxide.

Sleep- and time of day-linked RNA transcript expression in wild-type and IL1 receptor accessory protein-null mice.

Sleep regulation involves interleukin-1β (IL1) family members, TNF, and circadian clock genes. Previously, we characterized spontaneous sleep and sleep after 8 h of sleep deprivation (SD) ending at zeitgeber time (ZT)4 and ZT16 in wild-type (WT) and IL1 receptor accessory protein (AcP)- and brain-specific AcP (AcPb)-knockout (KO) mice. Here, we applied quantitative reverse transcriptase polymerase chain reaction and Spearman gene pair expression correlation methods to characterize , IL1 receptor 1 (), , Period 1 (), , adenosine deaminase (), peptidoglycan recognition protein 1 (), and mRNA expressions under conditions with distinct sleep phenotypes.

Interleukin-1 receptor accessory proteins are required for normal homeostatic responses to sleep deprivation.

Interleukin-1β (IL1) is a sleep regulatory substance. The IL1/IL1 type 1 receptor complex requires a receptor accessory protein (AcP) to signal. There are three isoforms of AcP.

The neuron-specific interleukin-1 receptor accessory protein alters emergent network state properties .

Small neuronal/glial networks exhibit sleep-like states. Sleep regulatory substance interleukin-1β (IL1) signals via its type I receptor and a receptor accessory protein (AcP). AcP has a neuron-specific isoform called AcPb.

Local sleep.

The historic sleep regulatory paradigm invokes "top-down" imposition of sleep on the brain by sleep regulatory circuits. While remaining conceptually useful, many sleep phenomena are difficult to explain using that paradigm, including, unilateral sleep, sleep-walking, and poor performance after sleep deprivation. Further, all animals sleep after non-lethal brain lesions, regardless of whether the lesion includes sleep regulatory circuits, suggesting that sleep is a fundamental property of small viable neuronal/glial networks.

Tumor necrosis factor alpha in sleep regulation.

This review details tumor necrosis factor alpha (TNF) biology and its role in sleep, and describes how TNF medications influence sleep/wake activity. Substantial evidence from healthy young animals indicates acute enhancement or inhibition of endogenous brain TNF respectively promotes and inhibits sleep. In contrast, the role of TNF in sleep in most human studies involves pathological conditions associated with chronic elevations of systemic TNF and disrupted sleep.

Interleukin 37 expression in mice alters sleep responses to inflammatory agents and influenza virus infection.

Multiple interactions between the immune system and sleep are known, including the effects of microbial challenge on sleep or the effects of sleep loss on facets of the immune response. Cytokines regulate, in part, sleep and immune responses. Here we examine the role of an anti-inflammatory cytokine, interleukin-37 (IL-37) on sleep in a mouse strain that expresses human IL-37b (IL37tg mice).

Microbial Products and Cytokines in Sleep and Fever Regulation.

Excessive sleepiness and fever are constitutional symptoms associated with systemic infection. Although fevers have been investigated for many years, sleep responses to infectious challenge have only recently been investigated. Inoculation of animals with bacterial, viral, protozoan and fungal organisms result in complex sleep responses dependent upon the microbial agent and route of administration.

P2X7 receptors in body temperature, locomotor activity, and brain mRNA and lncRNA responses to sleep deprivation.

The ionotropic purine type 2X7 receptor (P2X7R) is a nonspecific cation channel implicated in sleep regulation and brain cytokine release. Many endogenous rhythms covary with sleep, including locomotor activity and core body temperature. Furthermore, brain-hypothalamic cytokines and purines play a role in the regulation of these physiological parameters as well as sleep.

Voluntary Sleep Loss in Rats.

Study Objectives: Animal sleep deprivation (SDEP), in contrast to human SDEP, is involuntary and involves repeated exposure to aversive stimuli including the inability of the animal to control the waking stimulus. Therefore, we explored intracranial self-stimulation (ICSS), an operant behavior, as a method for voluntary SDEP in rodents.

Methods: Male Sprague-Dawley rats were implanted with electroencephalography/electromyography (EEG/EMG) recording electrodes and a unilateral bipolar electrode into the lateral hypothalamus.

Sleep function: Toward elucidating an enigma.

Sleep function remains controversial. Individual perspectives frame the issue of sleep function differently. We briefly illustrate how sleep measurement and the evolution, tissue organization levels, molecular mechanisms, and regulation of sleep could influence one's view of sleep function.

Tumor necrosis factor enhances the sleep-like state and electrical stimulation induces a wake-like state in co-cultures of neurons and glia.

We characterise sleep-like states in cultured neurons and glia during development in vitro as well as after electrical stimulation, the addition of tumor necrosis factor alpha (TNF), and the combination of TNF plus electrical stimulation. We also characterise optogenetic stimulation-induced ATP release and neuronal interleukin-1 and TNF expression in vitro demonstrating the activity dependence of these putative sleep-regulatory substances. Action potential (AP) burstiness, expressed as the burstiness index (BI), synchronization of slow electrical potentials between recording electrodes (SYN), and slow wave (SW) power (0.

Sleep deprivation and time-on-task performance decrement in the rat psychomotor vigilance task.

Study Objectives: The rat psychomotor vigilance task (rPVT) was developed as a rodent analog of the human psychomotor vigilance task (hPVT). We examined whether rPVT performance displays time-on-task effects similar to those observed on the hPVT.

Design: The rPVT requires rats to respond to a randomly presented light stimulus to obtain a water reward.

The neuron-specific interleukin-1 receptor accessory protein is required for homeostatic sleep and sleep responses to influenza viral challenge in mice.

Interleukin-1β (IL1) is involved in sleep regulation and sleep responses induced by influenza virus. The IL1 receptor accessory protein (AcP) and an alternatively spliced isoform of AcP found primarily in neurons, AcPb, form part of the IL1 signaling complex. IL1-induced sleep responses depend on injection time.

Sickness behaviour after lipopolysaccharide treatment in ghrelin deficient mice.

Ghrelin is an orexigenic hormone produced mainly by the gastrointestinal system and the brain. Much evidence also indicates a role for ghrelin in sleep and thermoregulation. Further, ghrelin was recently implicated in immune system modulation.

Olfactory bulb and hypothalamic acute-phase responses to influenza virus: effects of immunization.

Background: Within hours of intranasal challenge, mouse-adapted H1N1 A/Puerto Rico/8/34 (PR8) influenza genomic RNA is found in the olfactory bulb (OB) and OB pro-inflammatory cytokines are up-regulated. Severing the olfactory tract delays the acute-phase response (APR) and the APR is attenuated by immunization.

Objectives: To determine if immunization affects OB localization of influenza or the molecular brain mechanisms regulating APR.

Vagotomy attenuates brain cytokines and sleep induced by peripherally administered tumor necrosis factor-α and lipopolysaccharide in mice.

Study Objective: Systemic tumor necrosis factor-α (TNF-α) is linked to sleep and sleep altering pathologies in humans. Evidence from animals indicates that systemic and brain TNF-α have a role in regulating sleep. In animals, TNF-α or lipopolysaccharide (LPS) enhance brain pro-inflammatory cytokine expression and sleep after central or peripheral administration.

Sleep: a synchrony of cell activity-driven small network states.

We posit a bottom-up sleep-regulatory paradigm in which state changes are initiated within small networks as a consequence of local cell activity. Bottom-up regulatory mechanisms are prevalent throughout nature, occurring in vastly different systems and levels of organization. Synchronization of state without top-down regulation is a fundamental property of large collections of small semi-autonomous entities.

Sleep and immune function: glial contributions and consequences of aging.

The reciprocal interactions between sleep and immune function are well-studied. Insufficient sleep induces innate immune responses as evidenced by increased expression of pro-inflammatory mediators in the brain and periphery. Conversely, immune challenges upregulate immunomodulator expression, which alters central nervous system-mediated processes and behaviors, including sleep.