Nicotinic Mitigation of Neuroinflammation and Oxidative Stress After Chronic Sleep Deprivation

Xue, Rong; Wan, Yahui; Sun, Xiaoqian; Zhang, Xuan; Gao, Wei; Wu, Wei

doi:10.3389/fimmu.2019.02546

Cited by 77 publications

(60 citation statements)

References 55 publications

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“…In our patients we detected a significantly reduction of choline and BuChE activity and α7nAChR expression pointing out that non-neuronal cholinergic system may be associated with OSA. Our results are in accord with the study of Xue et al that in mice subjected to sleep disturbances detected a down-regulation of α7nAChR and an increase of pro-inflammatory cytokines in microglia and astrocytes [25]. In our OSA patients we detected a weak or absent correlation between α7nAChR expression and inflammatory cytokines.…”

Section: Discussionsupporting

confidence: 93%

Cholinergic Markers and Cytokines in OSA Patients

Reale

Velluto²,

Nicola

et al. 2020

IJMS

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The role of inflammation and dysfunction of the cholinergic system in obstructive sleep apnea (OSA) has not exhaustively clarified. Thus, in this study, we explore the non-neuronal cholinergic system and the balance of T helper (Th) 17- and T regulatory (Treg)-related cytokines in OSA patients. The study includes 33 subjects with obstructive sleep apnea and 10 healthy controls (HC). The expression levels of cholinergic system component, RAR-related orphan receptor (RORc), transcription factor forkhead box protein 3 (Foxp3) and cytokines were evaluated. Th17- and Treg-related cytokines, choline levels and acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) activity were quantified in OSA and control subjects. AChE and nicotinic receptor α 7 subunit (α7nAChR) gene expression and serum levels of choline, AChE and BuChE were lower in OSA patients than in the HC group. Compared with the HC group, OSA patients exhibited an increased expression, secretion and serum levels of pro-inflammatory cytokines, a reduced expression, secretion and serum levels of transforming growth factor (TGF)β and reduced Foxp3 mRNA levels. The Th17/Treg-related cytokine ratio was higher in the OSA group. Our results confirm and reinforce the hypothesis that OSA may be considered a systemic inflammatory disease, and that an imbalance of non-neuronal cholinergic and pro/anti-inflammatory cytokines may contribute to development and progression of comorbidities in OSA subjects. The evaluation of Th17/Treg-related cytokine may provide an additional explanation for OSA pathogenesis and clinical features, opening new directions for the OSA management.

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Section: Discussionsupporting

confidence: 93%

Cholinergic Markers and Cytokines in OSA Patients

Reale

Velluto²,

Nicola

et al. 2020

IJMS

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“…One such hypothesis focuses on the reduced expression of genes that occurs during adaptive response to stress. In line with this theory, 7 days of sleep deprivation was found to attenuate the expression of transcriptor Nrf-2 ( Xue et al, 2019 ), a transcription factor modulating basal and inducible expression of several antioxidant and detoxification enzymes, such as superoxide dismutase and catalase ( Rodrigues et al, 2018 ). Sleep deprivation has also been reported to result in an inefficient response of cellular scavenger mechanisms to reactive species, accompanied by a reduction in the activity of mitochondrial membrane binding protein sirtuin type 3 to upregulate antioxidant defenses ( Zhang et al, 2014 ).…”

Section: Sleep–wake Disruption Is a Contributing Factor To The Pathogmentioning

confidence: 76%

Molecular Mechanisms Underlying Reciprocal Interactions Between Sleep Disorders and Parkinson’s Disease

Yang

Zhang

et al. 2021

Front. Neurosci.

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Sleep–wake disruptions are among the most prevalent and burdensome non-motor symptoms of Parkinson’s disease (PD). Clinical studies have demonstrated that these disturbances can precede the onset of typical motor symptoms by years, indicating that they may play a primary function in the pathogenesis of PD. Animal studies suggest that sleep facilitates the removal of metabolic wastes through the glymphatic system via convective flow from the periarterial space to the perivenous space, upregulates antioxidative defenses, and promotes the maintenance of neuronal protein homeostasis. Therefore, disruptions to the sleep–wake cycle have been associated with inefficient metabolic clearance and increased oxidative stress in the central nervous system (CNS). This leads to excessive accumulation of alpha-synuclein and the induction of neuronal loss, both of which have been proposed to be contributing factors to the pathogenesis and progression of PD. Additionally, recent studies have suggested that PD-related pathophysiological alterations during the prodromal phase disrupt sleep and circadian rhythms. Taken together, these findings indicate potential mechanistic interactions between sleep–wake disorders and PD progression as proposed in this review. Further research into the hypothetical mechanisms underlying these interactions would be valuable, as positive findings may provide promising insights into novel therapeutic interventions for PD.

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“…It was shown that chronic sleep deprivation inhibits Akt phosphorylation and increases glycogen synthase kinase phosphorylation in the hippocampus. Furthermore, those changes occurred in conjunction with increased levels of pro-inflammatory factors (IFN-γ, TNF-α, monocyte chemoattractant protein-1 and IL-1β) as well as decreased levels of anti-inflammatory factors, www.nature.com/scientificreports/ the transcription factor nuclear factor erythroid 2-related factor 2 and the antioxidant enzyme HMOX1 46 . For example, during the time course of midazolam-induced hypnosis in mice, phosphorylated Akt1 levels markedly increase in the brain cortex, which suggests that Akt1 is involved in sleep-induced neuroplasticity 47 .…”

Section: Discussionmentioning

confidence: 99%

Uncovering the pharmacological mechanism of the effects of the Banxia-Xiakucao Chinese Herb Pair on sleep disorder by a systems pharmacology approach

Guo

Lou

et al. 2020

Sci Rep

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Sleep disorder (SD) has a high incidence and seriously affects quality of life, mental health and even the manifestation of physical diseases. The combination of Pinellia ternata (Chinese name: banxia) and Prunella vulgaris (Chinese name: xiakucao), known as the Banxia–Xiakucao Chinese herb pair (BXHP), is a proven Chinese herbal medicine that has been used to treat SD for thousands of years due to its significant clinical effects. However, its active pharmacological components and sedative–hypnotic mechanisms have not been fully elucidated. Thus, the present study used a systematic pharmacological approach to develop pharmacokinetic screens and target predictions via construction of a protein–protein interaction network and annotation database for SD-related and putative BXHP-related targets. Visualization, screening and integrated discovery enrichment analyses were conducted. The BXHP chemical database contains 166 compounds between the two herbal ingredients, and of these, 22 potential active molecules were screened by pharmacokinetic evaluation. The targets of 114 of the active molecules were predicted, and 34 were selected for further analysis. Finally, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses suggested that BXHP can reduce inflammatory responses. and mediate immune-related and central nervous system neurotransmitters via regulation of multiple targets and pathways. The use of a systematic pharmacology-based approach in the present study further elucidated the mechanisms of action underlying BXHP for the treatment of SD from a holistic perspective and sheds light on the systemic mechanisms of action of Chinese herbal medicines in general.

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Nicotinic Mitigation of Neuroinflammation and Oxidative Stress After Chronic Sleep Deprivation

Cited by 77 publications

References 55 publications

Cholinergic Markers and Cytokines in OSA Patients

Cholinergic Markers and Cytokines in OSA Patients

Molecular Mechanisms Underlying Reciprocal Interactions Between Sleep Disorders and Parkinson’s Disease

Uncovering the pharmacological mechanism of the effects of the Banxia-Xiakucao Chinese Herb Pair on sleep disorder by a systems pharmacology approach

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