Modafinil Reduces Neuronal Pyroptosis and Cognitive Decline After Sleep Deprivation

Xiong, Xiangyang; Zuo, Yan; Cheng, Lü; Yin, Zhenyu; Hu, Tianpeng; Guo, Mengtian; Han, Zhaoli; Ge, Xintong; Li, Wenzhu; Wang, Yan; Wang, Dong; Wang, Conglin; Zhang, Lan; Zhang, Yaodan; Liu, Qiang; Chen, Fanglian; Lei, Ping

doi:10.3389/fnins.2022.816752

Cited by 10 publications

(7 citation statements)

References 36 publications

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“…However, NLRP3 inflammasome was expressed in a variety of cells, including astrocytes [ 38 ], endothelial cells [ 39 ], neutrophils and monocytes [ 20 ]. Moreover, our previous study has confirmed the promotion of neuronal pyroptosis under conditions of sleep deprivation [ 40 ]. Similarly, the assembly and activation of the NLRP3 inflammasome in dopamine neurons is also an important strategy to prevent the degeneration of neurons.…”

Section: Discussionmentioning

confidence: 74%

“…So far, it seems impossible to distinguish whether inflammatory cytokines in brain tissue are produced by microglia, neurons or other nerve cells. Levels of neuronal inflammatory cytokines have been studied in traumatic brain injury and sleep deprivation [ 40 , 63 ]. We cannot deny that miR-146a-5p affected the secretion of inflammatory cytokines in microglia cells.…”

Section: Discussionmentioning

confidence: 99%

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Microglial exosomes alleviate intermittent hypoxia-induced cognitive deficits by suppressing NLRP3 inflammasome

et al. 2023

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Intermittent hypoxia is the best predictor of developing cognitive decline and Alzheimer’s disease progression in patients with obstructive sleep apnea. The nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome has been poorly studied as a regulator of neuroinflammation in cognitive impairment caused by intermittent hypoxia. As critical inflammatory cells, exosomes secreted by microglia have been found to affect the spread of pathologic proteins and neuropathology in neurodegenerative diseases. However, the effects of microglial exosomes on neuroinflammation and cognitive outcomes after intermittent hypoxia remain unclear. In this study, the role of miRNAs in microglial exosomes in improving cognitive deficits in mice exposed to intermittent hypoxia was investigated. We demonstrated that miR-146a-5p fluctuated over time in microglial exosomes of mice exposed to intermittent hypoxia for different periods of time, which could regulate neuronal NLRP3 inflammasome and neuroinflammation. In primary neurons, we found that miR-146a-5p regulated mitochondrial reactive oxygen species by targeting HIF1α, thus affecting the NLRP3 inflammasome and secretion of inflammatory factors. Similarly, further studies showed that inhibition of NLRP3 by administering overexpressed miR-146a-5p in microglial exosomes and MCC950 has improved neuroinflammation and cognitive dysfunction in mice after intermittent hypoxia. In conclusion, NLRP3 inflammasome may be a regulatory target for ameliorating cognitive impairment caused by intermittent hypoxia, and microglial exosomal miR-146a-5p may be a promising therapeutic strategy.

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Section: Discussionmentioning

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Microglial exosomes alleviate intermittent hypoxia-induced cognitive deficits by suppressing NLRP3 inflammasome

et al. 2023

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“…Modafinil is a widely-used stimulant that was originally developed to treat paroxysmal narcolepsy. According to different research studies, modafinil improves NLRs inflammasome-mediated pyroptosis in mice with SD through increasing BDNF (brain-derived neurotrophic factor) stimulation in the hippocampus and synaptic plasticity, which in turn, improve learning, memory, and cognitive functions (Xiong et al, 2022). Signaling pathways of Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome.…”

Section: Sd-induced Cognitive Decline: Targeting Nlrp3 Inflammasomementioning

confidence: 99%

“…Targeting the regulation of impaired neuronal pyroptosis and neuroinflammation may be a promising therapeutic strategy for treatment of SD. (Xiong et al, 2022) 9…”

Section: # Findings Referencesmentioning

confidence: 99%

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

et al. 2022

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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.

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“…The pathogenesis of SD associated with cognitive disorders is not very clear at present, in modern medicine, awakening promoters, and receptor inhibitors are the main drugs to promote sleep and improve cognition. [ 8 , 9 ] Although these drugs can extend the patients’ sleep time and improve cognition, they cannot solve the underlying problem of sleep deficiency and have great side effects in the long term. As the treasure of China, traditional Chinese acupuncture has a long history, safety, and effectiveness, and has been widely respected in clinical application.…”

Section: Introductionmentioning

confidence: 99%

Study on acupuncture improving sleep deprivation comorbid with cognitive dysfunction based on rs-fMRI: A protocol for systematic review and meta-analysis

Guo¹,

Yang²,

Wang³

et al. 2023

Medicine

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Background: Sleep deprivation often lead to changes in attention, memory, mood, alertness, and metabolism. Especially, it is often accompanied by cognitive impairment of the brain. Acupuncture is safe and effective for improving cognitive function, but its underlying mechanism is not fully understood. Resting-state functional magnetic resonance imaging is an important means to study brain activity changes. However, the results are inconsistent and lack systematic evaluation and analysis. Methods: We will search 9 databases, including PubMed, EMBASE, EBSCOhost-Medline, Web of Science, Cochrane Library, China National Knowledge Infrastructure, VIP Database and Wan-Fang Database, Chinese Biomedical Literature Database, and 2 clinical trials register platforms: Chinese Clinical Trial Registry, ClinicalTrials.gov ( www.ClinicalTrials.gov/ ) from inception to November 1, 2022. We will use the Review Manager 5.4 software provided by the Cochrane Collaborative Network for statistical analysis. We then assessed the quality and risk of the included studies and observed the outcome measures. Results: This study will analyze the effect of acupuncture on brain activity changes, improvement of sleep duration, and cognitive impairment. Conclusion: This meta-analysis aims to investigate the efficacy of acupuncture on brain activity changes in sleep deprivation comorbid with cognitive dysfunction, so as to provide effective evidence for clarifying its pathogenesis.

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Modafinil Reduces Neuronal Pyroptosis and Cognitive Decline After Sleep Deprivation

Cited by 10 publications

References 36 publications

Microglial exosomes alleviate intermittent hypoxia-induced cognitive deficits by suppressing NLRP3 inflammasome

Microglial exosomes alleviate intermittent hypoxia-induced cognitive deficits by suppressing NLRP3 inflammasome

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

Study on acupuncture improving sleep deprivation comorbid with cognitive dysfunction based on rs-fMRI: A protocol for systematic review and meta-analysis

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