Cytokines in immune function and sleep regulation

Krueger, James M.; Majde, Jeannine A.; Rector, David M.

doi:10.1016/b978-0-444-52006-7.00015-0

Cited by 103 publications

(79 citation statements)

References 157 publications

(181 reference statements)

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“…Through mechanisms that remain to be clearly understood, this binding results in proteolytic processing and release of inflammatory cytokines. 4,16,56,67,68 Given this understanding, how might an increased generation of protein fragments during wakefulness-the proposed molecular cause of sleep-interact with ATP/cytokine pathways?…”

Section: Relationship Of Protein Fragments To Other Somnogensmentioning

confidence: 99%

“…56,65,66 As described below, these and other inflammatory cytokines can act as somnogens, indicating a major but incompletely understood connection between the immune system and sleep. 4,16,29,31,36,[67][68][69][70][71][72][73][74][75][76][77][78][79] Another potent endogenous somnogen is the PGD 2 prostaglandin, which preferentially induces NREM sleep. 11,28,80,81 The somnogenic activity of PGD 2 is mediated at least in part by the ability of brain-produced PGD 2 to increase the concentration of extracellular adenosine.…”

Section: Introductionmentioning

confidence: 99%

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Augmented generation of protein fragments during wakefulness as the molecular cause of sleep: a hypothesis

Varshavsky

2012

Protein Science

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Despite extensive understanding of sleep regulation, the molecular-level cause and function of sleep are unknown. I suggest that they originate in individual neurons and stem from increased production of protein fragments during wakefulness. These fragments are transient parts of protein complexes in which the fragments were generated. Neuronal Ca 21 fluxes are higher during wakefulness than during sleep. Subunits of transmembrane channels and other proteins are cleaved by Ca 21 -activated calpains and by other nonprocessive proteases, including caspases and secretases. In the proposed concept, termed the fragment generation (FG) hypothesis, sleep is a state during which the production of fragments is decreased (owing to lower Ca 21 transients) while fragment-destroying pathways are upregulated. These changes facilitate the elimination of fragments and the remodeling of protein complexes in which the fragments resided. The FG hypothesis posits that a proteolytic cleavage, which produces two fragments, can have both deleterious effects and fitness-increasing functions. This (previously not considered) dichotomy can explain both the conservation of cleavage sites in proteins and the evolutionary persistence of sleep, because sleep would counteract deleterious aspects of protein fragments. The FG hypothesis leads to new explanations of sleep phenomena, including a longer sleep after sleep deprivation. Studies in the 1970s showed that ethanol-induced sleep in mice can be strikingly prolonged by intracerebroventricular injections of either Ca 21 alone or Ca 21 and its ionophore (Erickson et al., Science 1978;199:1219-1221 Harris, Pharmacol Biochem Behav 1979;10:527-534; Erickson et al., Pharmacol Biochem Behav 1980;12:651-656). These results, which were never interpreted in connection to protein fragments or the function of sleep, may be accounted for by the FG hypothesis about molecular causation of sleep.

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Section: Relationship Of Protein Fragments To Other Somnogensmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Augmented generation of protein fragments during wakefulness as the molecular cause of sleep: a hypothesis

Varshavsky

2012

Protein Science

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“…In addition, cytokines are responsible for inflammation-induced sleep enhancement (Krueger, 2008;Krueger et al, 1986Krueger et al, , 2011 and increased seizure susceptibility (Vezzani, 2005;Vezzani et al, 2002Vezzani et al, , 2008a. Thus, it is also an interesting topic to elucidate the relationship between the modification of the sleep-wake cycle by LPS treatment and increased frequency of seizures.…”

Section: Lps Administration-induced Signaling Leads To Extensive Metamentioning

confidence: 99%

Brain protein expression changes in WAG/Rij rats, a genetic rat model of absence epilepsy after peripheral lipopolysaccharide treatment

Győrffy

Kovács

Gulyássy

et al. 2014

Brain, Behavior, and Immunity

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a b s t r a c tPeripheral injection of bacterial lipopolysaccharide (LPS) facilitates 8-10 Hz spike-wave discharges (SWD) characterizing absence epilepsy in WAG/Rij rats. It is unknown however, whether peripherally administered LPS is able to alter the generator areas of epileptic activity at the molecular level. We injected 1 mg/kg dose of LPS intraperitoneally into WAG/Rij rats, recorded the body temperature and EEG, and examined the protein expression changes of the proteome 12 h after injection in the frontoparietal cortex and thalamus. We used fluorescent two-dimensional differential gel electrophoresis to investigate the expression profile. We found 16 differentially expressed proteins in the fronto-parietal cortex and 35 proteins in the thalamus. It is known that SWD genesis correlates with the transitional state of sleep-wake cycle thus we performed meta-analysis of the altered proteins in relation to inflammation, epilepsy as well as sleep. The analysis revealed that all categories are highly represented by the altered proteins and these protein-sets have considerable overlap. Protein network modeling suggested that the alterations in the proteome were largely induced by the immune response, which invokes the NFkB signaling pathway. The proteomics and computational analysis verified the known functional interplay between inflammation, epilepsy and sleep and highlighted proteins that are involved in their common synaptic mechanisms. Our physiological findings support the phenomenon that high dose of peripheral LPS injection increases SWD-number, modifies its duration as well as the sleep-wake stages and decreases body temperature.

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“…Pain literature had shown than nocturnal pain disturbed sleep [147]. A subjective sleepiness can accompany the relative elevation of the levels of inflammatory mediators as part of immune dysregulation that is proposed to occur with low 25(OH) D [148]. Children with NE were observed to suffer from sleep fragmentation [149] Therefore, it is plausible to assume that low vitamin D is associated with poor sleep quality including sleep fragmentation in children with SCA that leads to NE.…”

Section: Vitamin Dmentioning

confidence: 99%

Nocturnal Enuresis in Children and Adolescent with Sickle cell Anemia

Ahmed¹

2017

Med Surg Urol

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Children with sickle cell anemia (SCA) have a tendency to have nocturnal enuresis (NE) more than normal children with males being more affected than females. Mechanisms of NE that operate in normal children probably do so in children with SCA. Postulated causes of nocturnal enuresis in individuals with SCA include hyposthenuria causing nocturnal polyuria, reduced bladder capacity or nocturnal bladder overactivity, sleep disordered breathing and an increased arousal thresholds. The variation in the reported prevalence rate of NE in SCA is probably due to differences in definition criteria and methodology. This review will discuss the prevalence rate and postulated causes of NE in children with SCA.

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Cytokines in immune function and sleep regulation

Cited by 103 publications

References 157 publications

Augmented generation of protein fragments during wakefulness as the molecular cause of sleep: a hypothesis

Augmented generation of protein fragments during wakefulness as the molecular cause of sleep: a hypothesis

Brain protein expression changes in WAG/Rij rats, a genetic rat model of absence epilepsy after peripheral lipopolysaccharide treatment

Nocturnal Enuresis in Children and Adolescent with Sickle cell Anemia

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