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

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.

Ganoderma lucidum spore extract improves sleep disturbances in a rat model of sporadic Alzheimer’s disease

“…A wide range of stimulations that appear during tissue damage, resulting in NLRP3 activation and formation of an inflammasome complex and finally induces the secretion of activated cytokines and results inflammatory responses. NLRP3 inflammasome signaling is a characteristic of sleep disorders and AD pathophysiology ( Milner et al, 2021 ; Amini et al, 2022 ). Studies have shown that sleep deprivation activates the NLRP3 inflammasome and causes neuroinflammation in the rat brain ( Smith et al, 2021 ).…”

The relationship between sleep and innate immunity

“…Additionally, sleep disturbances are associated with the hypothalamic-pituitary-adrenal axis and inflammatory cytokines such as IL-6 and TNF-α [16]. Inflammasomes, in particular, the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, are related to short sleep duration [17].…”

“…Inflammasomes are complexes of receptors and sensors of the innate immune response. NLRP3 is one of the well-recognized inflammasomes that is activated by pathogen-associated molecular patterns and danger-associated molecular patterns, initiates inflammatory responses by enhancing proinflammatory cytokines, and activates NF-κB signaling pathways [17]. In a study with chronic insomnia patients with objectively determined short sleep duration, the NLRP3 inflammasome was upregulated compared to healthy controls.…”

Neutrophil-to-lymphocyte ratio as a predictive biomarker for early diagnosis of depression: A narrative review

“…Depressed mood, lack of interest or pleasure, decreased energy, feelings of guilt or low self-worth, interrupted sleep or food, and impaired concentration are all signs of depression, a potentially fatal condition. It can occur at any age from childhood to late life and is a tremendous cost to society as this disorder causes severe distress and disruption of life and, if left untreated, it can cause suicidal thoughts and the death of 800,000 people annually around the world, according to confirmed statistics ( Mehdi et al, 2023 ; Brigitta, 2022 ; Amini et al, 2022 ). Depression is currently thought to impact 350 million people worldwide, and by 2030, it is anticipated to be the major cause of disease burden in high-income nations ( Thati et al, 2023 ; Seid et al, 2020 ).…”

“…Its clinical effectiveness and dependability are highly encouraging and superior to other newly developed multiparameter approaches ( Smith et al, 2013 ). The advantages of having an objective and aetiologically sound panel of biomarkers for depression are substantial: ( Mehdi et al, 2023 ) their existence can be used to predict the likelihood of onset or presence of the disorder; ( Brigitta, 2022 ) they can be used to stratify the disorder according to severity and symptomatology; ( Amini et al, 2022 ) they can be used as an indicator of disease prognosis; and ( Thati et al, 2023 ) they can be used to predict response and track progress after a therapeutic intervention ( Bohnert, 2021 ). Previous studies have indicated that inflammation is crucial for the emergence of depression.…”