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Review
. 2022 Dec 22:16:1018628.
doi: 10.3389/fnins.2022.1018628. eCollection 2022.

Sleep deprivation and NLRP3 inflammasome: Is there a causal relationship?

Mohammad Amini  1 , Zahra Yousefi  2 , Sayed Soran Ghafori  1 , Gholamreza Hassanzadeh  1
Affiliations
Review

Sleep deprivation and NLRP3 inflammasome: Is there a causal relationship?

Mohammad Amini et al. Front Neurosci. .

Abstract

In the modern era, sleep deprivation (SD) is one of the most common health problems that has a profound influence on an individual's quality of life and overall health. Studies have identified the possibility that lack of sleep can stimulate inflammatory responses. NLRP3 inflammasome, a key component of the innate immune responses, initiates inflammatory responses by enhancing proinflammatory cytokine release and caspase-1-mediated pyroptosis. In this study, NLRP3 modification, its proinflammatory role, and potential targeted therapies were reviewed with regard to SD-induced outcomes. A growing body of evidence has showed the importance of the mechanistic connections between NLRP3 and the detrimental consequences of SD, but there is a need for more clinically relevant data. In animal research, (i) some animals show differential vulnerability to the effects of SD compared to humans. (ii) Additionally, the effects of sleep differ depending on the SD technique employed and the length of SD. Moreover, paying attention to the crosstalk of all the driving factors of NLRP3 inflammasome activation such as inflammatory responses, autonomic control, oxidative stress, and endothelial function is highly recommended. In conclusion, targeting NLRP3 inflammasome or its downstream pathways for therapy could be complicated due to the reciprocal and complex relationship of SD with NLRP3 inflammasome activation. However, additional research is required to support such a causal claim.

Keywords: inflammasome; inflammation; neuroinflammation; sleep; sleep deprivation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Sleep-controlling neural networks. Different types of sleep are attributed to a brain-wide neural network. Non-REM (NREM) sleep-promoting centers include the ventrolateral preoptic region, basal forebrain regions, the parafacial zone, and cortical sleep-active neurons. Neuronal networks in the brainstem, including the sublaterodorsal nucleus (SLD), pedunculopontine nucleus (PPT), and laterodorsal tegmental nucleus (LDTg), are involved in inducing rapid eye movement (REM) sleep.
FIGURE 2
FIGURE 2
Signaling pathways of Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. The first signal (priming: left) initiated through engagement of pathogen-associated molecular pattern (PAMPs) and danger-associated molecular patterns (DAMPs) with different pattern recognition receptors (PRRs), which in turn leading to activation of nuclear factor κB (NF-κB) and gene transcriptional of NLRP3 components, and pro inflammatory cytokines pro-IL-1 and pro-IL-18. The secondary signal (activation: right) is provided by a wide range of PAMPs and DAMPs that leading to formation of NLRP3 inflammasome complex. This complex activates caspase 1 enzyme, which resulting cleaves and secretion of activate forms of pro-IL-1 and pro-IL-18 as well as inducing cell death pyroptosis.
FIGURE 3
FIGURE 3
Possible mechanisms of Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation caused by sleep deprivation. Sleep deprivation can change neuromodulators and neuro-endocrines involved in sleep regulation and they could be altered during and after sleep deprivation. Together, these results demonstrated a priming signal for NLRP3 inflammasome activation by activating the NF-κB signaling pathway. EN, epinephrine; NE, norepinephrine; ROS, reactive oxygen species.
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References

    1. Aghelan Z., Abtahi S. H., Khazaie H., Bahrehmand F., Khodarahmi R. (2022). Increased peripheral NLRP3 gene expression is associated with the reduced duration of rapid eye movements sleep and sleep continuity in chronic insomnia patients. Scand. J. Sleep Med. 1 137–139.
    1. Amini M., Saboory E., Pourheydar B., Bagheri M., Naderi R. (2020b). International immunopharmacology involvement of endocannabinoid system, in fl ammation and apoptosis in diabetes induced liver injury: Role of 5-HT3 receptor antagonist. Int. Immunopharmacol. 79:106158. 10.1016/j.intimp.2019.106158 - DOI - PubMed
    1. Amini M., Saboory E., Derafshpour L., Fakhari A., Wu J. C., Bruggeman R., et al. (2020a). The impact of sleep deprivation on sexual behaviors and FAAH expression in the prefrontal cortex of male rats. Neurosci. Lett. 735:135254. 10.1016/j.neulet.2020.135254 - DOI - PubMed
    1. Antza C., Kostopoulos G., Mostafa S., Nirantharakumar K., Tahrani A. (2022). The links between sleep duration, obesity and type 2 diabetes mellitus. J. Endocrinol. 252 125–141. 10.1530/JOE-21-0155 - DOI - PMC - PubMed
    1. Bazrafkan M., Nikmehr B., Shahverdi A., Hosseini S. R., Hassani F., Poorhassan M., et al. (2018). FULL LENGTH iranian biomedical lipid peroxidation and its role in the expression of NLRP1a and NLRP3 genes in testicular tissue of male rats: A model of spinal cord injury. Iran. Biomed. J. 22 151–159. 10.22034/ibj.22.3.151 - DOI - PMC - PubMed

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