ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Extended wakefulness: compromised metabolics in and degeneration of locus ceruleus neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 167 citations in OpenAlex.
- Targeting Specific Sirtuin Modulation: Emerging Therapeutic Strategies for Healthy Cognitive Ageing and Potential Implications for Alzheimer's Disease.Molecules (Basel, Switzerland) · 2026Review
- The role of sleep disorders in orchestrating proteomic dysfunction and multi-morbidity.Molecular psychiatry · 2026Review
- Chronic Sleep Disturbance Enhances Inflammation and Collagen Production in Neural- and Myofascial Tissues in Uninjured Rats.International journal of molecular sciences · 2026Article
- Insomnia: the gut microbiome connection, prospects for probiotic and postbiotic therapies, and future directions.Journal of advanced research · 2026Review
- Changed Serum Levels of Sirtuin1 and Sirtuin3 and Their Correlations with Sleep Quality and Cognitive Function in Patients with Chronic Insomnia Disorder.Nature and science of sleep · 2026Article
- Sleep is a therapeutic window for photostimulation of drainage of aging brain.Frontiers of optoelectronics · 2025Article
- The Ability of Activity and Cognition in Old Mice to Predict Age of Death.Aging and disease · 2025Article
- Concussion and the Autonomic, Immune, and Endocrine Systems: An Introduction to the Field and a Treatment Framework for Persisting Symptoms.Journal of personalized medicine · 2025Review
- Associations between night/shift working and late-life brain health.Brain communications · 2025Article
- Norepinephrine Drives Sleep Fragmentation Activation of Asparagine Endopeptidase, Locus Ceruleus Degeneration, and Hippocampal Amyloid-βThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- A neuron-glia lipid metabolic cycle couples daily sleep to mitochondrial homeostasis.Nature neuroscience · 2024Article
- Article
- Locus Coeruleus and Noradrenergic Pharmacology in Neurodegenerative Disease.Handbook of experimental pharmacology · 2024Review
- Acute sleep deprivation in mice generates protein pathology consistent with neurodegenerative diseases.Frontiers in neuroscience · 2024Article
- Activation of Basal Forebrain Astrocytes Induces Wakefulness without Compensatory Changes in Sleep Drive.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Improvement of neurological recovery in the insomnia rats by Warming Yang Strategy through targeting SIRT4 by inhibiting inflammation and apoptosis.Immunity, inflammation and disease · 2023Article
- Effect of N-Acetylcysteine on Sleep: Impacts of Sex and Time of Day.Antioxidants (Basel, Switzerland) · 2023Article
- Proteostasis failure exacerbates neuronal circuit dysfunction and sleep impairments in Alzheimer's disease.Molecular neurodegeneration · 2023Review
- Mu-opioid receptor-expressing neurons in the paraventricular thalamus modulate chronic morphine-induced wake alterations.Translational psychiatry · 2023Article
- Loss of mitochondrial enzyme GPT2 causes early neurodegeneration in locus coeruleus.Neurobiology of disease · 2022Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
Abstract
Modern society enables a shortening of sleep times, yet long-term consequences of extended wakefulness on the brain are largely unknown. Essential for optimal alertness, locus ceruleus neurons (LCns) are metabolically active neurons that fire at increased rates across sustained wakefulness. We hypothesized that wakefulness is a metabolic stressor to LCns and that, with extended wakefulness, adaptive mitochondrial metabolic responses fail and injury ensues. The nicotinamide adenine dinucleotide-dependent deacetylase sirtuin type 3 (SirT3) coordinates mitochondrial energy production and redox homeostasis. We find that brief wakefulness upregulates SirT3 and antioxidants in LCns, protecting metabolic homeostasis. Strikingly, mice lacking SirT3 lose the adaptive antioxidant response and incur oxidative injury in LCns across brief wakefulness. When wakefulness is extended for longer durations in wild-type mice, SirT3 protein declines in LCns, while oxidative stress and acetylation of mitochondrial proteins, including electron transport chain complex I proteins, increase. In parallel with metabolic dyshomeostasis, apoptosis is activated and LCns are lost. This work identifies mitochondrial stress in LCns upon wakefulness, highlights an essential role for SirT3 activation in maintaining metabolic homeostasis in LCns across wakefulness, and demonstrates that extended wakefulness results in reduced SirT3 activity and, ultimately, degeneration of LCns.
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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.