ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2019
Cognition-Enhancing Vagus Nerve Stimulation Alters the Epigenetic Landscape.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- Daily biofeedback to modulate heart rate oscillations affects structural volume in hippocampal subregions targeted by the locus coeruleus in older adults but not younger adults.Neurobiology of aging · 2023Trial
- Transcutaneous Vagal Nerve Stimulation Alone or in Combination With Radiotherapy Stimulates Lung Tumor Infiltrating Lymphocytes But Fails to Suppress Tumor Growth.Frontiers in immunology · 2021Trial
- HDAC11 as a potential therapeutic target for Alzheimer's disease.Drug discovery today · 2026Review
- Neuromodulation in Neuro-Oncology: A Scoping Review.Journal of personalized medicine · 2026Review
- Vagus nerve stimulation modulates LPS-induced epileptogenicity: the role of inflammation suppression.Research square · 2026Article
- Cognitive neurobehavior and synaptic plasticity after vagus nerve stimulation in female rats: Interaction between estrous cycle and neurostimulation.Bioelectronic medicine · 2026Article
- Pairing extinction training with vagus nerve stimulation reduces drug-seeking by altering activity in afferents to the medial prefrontal cortex.Frontiers in neuroscience · 2026Article
- Gut microbiomes-host immune response and organ dysfunction across the gut-lung, gut-brain, and gut-liver axes.Frontiers in cellular and infection microbiology · 2026Review
- Therapeutic potential of vagus nerve stimulation in neurodegenerative diseases: research progress and mechanisms.Frontiers in immunology · 2026Review
- Vagus nerve-driven microbiota homeostasis: a promising integrative add-on therapy for neurodevelopmental disorders.Frontiers in neuroscience · 2026Article
- Sympathetic-parasympathetic system deregulation theory of aging.npj aging · 2025Review
- Transcutaneous cervical vagus nerve stimulation (tcVNS) does not enhance learning and memory performance in a visual detection task.Scientific reports · 2025Article
- Review
- Vagal Sensory Gut-Brain Pathways That Control Eating-Satiety and Beyond.Comprehensive physiology · 2025Review
- Vagus nerve stimulation (VNS) preventing postoperative cognitive dysfunction (POCD): two potential mechanisms in cognitive function.Molecular and cellular biochemistry · 2025Review
- Article
- Case Report: Peripheral combined central dual-target magnetic stimulation for non- motor symptoms of Parkinson's disease.Frontiers in psychiatry · 2025Article
- Vagus nerve stimulation ameliorates cognitive impairment caused by hypoxia.Frontiers in behavioral neuroscience · 2025Article
- A vagal route to memory: evidence from invasive and non-invasive electrical vagus nerve stimulation studies and areas for future clinical application.Frontiers in human neuroscience · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vagus nerve stimulation (VNS) has been shown to enhance learning and memory, yet the mechanisms behind these enhancements are unknown. Here, we present evidence that epigenetic modulation underlies VNS-induced improvements in cognition. We show that VNS enhances novelty preference (NP); alters the hippocampal, cortical, and blood epigenetic transcriptomes; and epigenetically modulates neuronal plasticity and stress-response signaling genes in male Sprague Dawley rats. Brain-behavior analysis revealed structure-specific relationships between NP test performance (NPTP) and epigenetic alterations. In the hippocampus, NPTP correlated with decreased histone deacetylase 11 (HDAC11), a transcriptional repressor enriched in CA1 cells important for memory consolidation. In the cortex, the immediate early gene (IEG) ARC was increased in VNS rats and correlated with transcription of plasticity genes and epigenetic regulators, including HDAC3. For rats engaged in NPTP, ARC correlated with performance. Interestingly, blood ARC transcripts decreased in VNS rats performing NPTP, but increased in VNS-only rats. Because DNA double-strand breaks (DSBs) facilitate transcription of IEGs, we investigated phosphorylated H2A.X (γH2A.X), a histone modification known to colocalize with DSBs. In agreement with reduced cortical stress-response transcription factor NF-κB1, chromatin immunoprecipitation revealed reduced γH2A.X in the ARC promoter. Surprisingly, VNS did not significantly reduce transcription of cortical or hippocampal proinflammatory cytokines. However, TNFRSF11B (osteoprotegerin) correlated with NPTP as well as plasticity, stress-response signaling, and epigenetic regulation transcripts in both hippocampus and cortex. Together, our findings provide the first evidence that VNS induces widespread changes in the cognitive epigenetic landscape and specifically affects epigenetic modulators associated with NPTP, stress-response signaling, memory consolidation, and cortical neural remodeling.
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What OpenQuestion holds
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.