ArticleJournal of cellular and molecular medicine2019
Molecular mechanism of tumour necrosis factor alpha regulates hypocretin (orexin) expression, sleep and behaviour.
Article in Journal of cellular and molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 2 of them syntheses that pooled it.
What it found
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The trial behind it
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Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it, 20 citations in OpenAlex.
- Sleep-neuroinflammation interactions in Alzheimer's disease: a systematic review of biomarker pathways.Frontiers in aging neuroscience · 2026Pooled it
- Orexin and Sleep Disturbances in Alpha-Synucleinopathies: a Systematic Review.Current neurology and neuroscience reports · 2024Pooled it
- Longitudinal Associations Between Inflammatory Biomarkers and Fatigue in Patients With Colorectal Cancer: A Multicenter Study.Cancer medicine · 2026Observational
- Cytokines in narcolepsy type 1: pathogenic relevance, biomarker potential, and future directions.Frontiers in neurology · 2026Review
- Hypoxia-Induced Gut-Brain Axis Remodeling and Insomnia: Mechanisms and Microbiota Adaptive Regulation from a Translational Perspective.Journal of inflammation research · 2026Review
- Human microglia reduce alpha-synuclein aggregation and are neuroprotective in adult mouse brain.Brain, behavior, and immunity · 2025Article
- Exploring the Role of Polyunsaturated Fatty Acids in Children's Sleep.Biomedicines · 2025Review
- Adipose Tissue Exosome circ_sxc Mediates the Modulatory of Adiposomes on Brain Aging by Inhibiting Brain dme-miR-87-3p.Molecular neurobiology · 2024Article
- Inclusion of hypocretin-1 improved performance of poor sleep quality prediction for elderly patients with acute ischemic stroke: a prospective cohort study.Frontiers in aging neuroscience · 2024Article
- α-Synuclein Induced the Occurrence of RBD via Interaction with OX1R and Modulated Its Degradation.Neuromolecular medicine · 2023Article
- Nanowired Delivery of Cerebrolysin Together with Antibodies to Amyloid Beta Peptide, Phosphorylated Tau, and Tumor Necrosis Factor Alpha Induces Superior Neuroprotection in Alzheimer's Disease Brain Pathology Exacerbated by Sleep Deprivation.Advances in neurobiology · 2023Review
- Review
- Cerebrospinal Fluid TNF-α and Orexin in Patients With Parkinson's Disease and Rapid Eye Movement Sleep Behavior Disorder.Frontiers in neurology · 2022Article
- Role of Vitamin E and the Orexin System in Neuroprotection.Brain sciences · 2021Review
- Cortical Transcriptomic Alterations in Association With Appetitive Neuropeptides and Body Mass Index in Posttraumatic Stress Disorder.The international journal of neuropsychopharmacology · 2021Article
- Polygenic risk score analysis revealed shared genetic background in attention deficit hyperactivity disorder and narcolepsy.Translational psychiatry · 2020Article
- Article
- Multiple Sclerosis: Melatonin, Orexin, and Ceramide Interact with Platelet Activation Coagulation Factors and Gut-Microbiome-Derived Butyrate in the Circadian Dysregulation of Mitochondria in Glia and Immune Cells.International journal of molecular sciences · 2019Review
- Molecular mechanism of tumour necrosis factor alpha regulates hypocretin (orexin) expression, sleep and behaviour.Journal of cellular and molecular medicine · 2019Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypocretin 1 and hypocretin 2 (orexin A and B) regulate sleep, wakefulness and emotion. Tumour necrosis factor alpha (TNF-α) is an important neuroinflammation mediator. Here, we examined the effects of TNF-α treatment on hypocretin expression in vivo and behaviour in mice. TNF-α decreased hypocretin 1 and hypocretin 2 expression in a dose-dependent manner in cultured hypothalamic neurons. TNF-α decreased mRNA stability of prepro-hypocretin, the single precursor of hypocretin 1 and hypocretin 2. Mice challenged with TNF-α demonstrated decreased expression of prepro-hypocretin, hypocretin 1 and hypocretin 2 in hypothalamus. In response to TNF-α, prepro-hypocretin mRNA decay was increased in hypothalamus. TNF-α neutralizing antibody restored the expression of prepro-hypocretin, hypocretin 1 and hypocretin 2 in vivo in TNF-α challenged mice, supporting hypocretin system can be impaired by increased TNF-α through decreasing hypocretin expression. Repeated TNF-α challenge induced muscle activity during rapid eye movement sleep and sleep fragmentation, but decreased learning, cognition and memory in mice. TNF-α neutralizing antibody blocked the effects of TNF-α; in contrast, hypocretin receptor antagonist enhanced the effects of TNF-α. The data support that TNF-α is involved in the regulation of hypocretin expression, sleep and cognition. The findings shed some lights on the role of neuroinflammation in neurodegenerative diseases including Alzheimer's disease and Parkinson's disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.