ArticleThe Journal of clinical investigation2013
Epigenetic changes induced by adenosine augmentation therapy prevent epileptogenesis.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers, 1 of them a synthesis that pooled it.
What it found
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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
160 citing papers in PubMed, 1 synthesis or guideline pooled it, 261 citations in OpenAlex.
- Purinergic system dysfunction in mood disorders: a key target for developing improved therapeutics.Progress in neuro-psychopharmacology & biological psychiatry · 2015Pooled it
- Shared Genetic Architecture Between Common Epilepsies and Subcortical Brain Volumes Is Associated With Cognition and Mental Health.CNS neuroscience & therapeutics · 2026Article
- Review
- Energy metabolism, adenosine, and glutamate signaling reprogramming by decanoic acid in Glut1 disorder syndrome.Epilepsia open · 2026Article
- Therapeutic Potential Target of Adenosine for Epilepsy: Focusing on Its Interaction with the Molecular Epileptogenic Network.Biomolecules · 2026Review
- Calponin-3 is associated with epilepsy through the regulation of astrocyte activity.Brain pathology (Zurich, Switzerland) · 2026Article
- Commonalities in gene expression and methylation changes across two rat models of acquired epilepsy.Scientific reports · 2026Article
- Antecedent enhancer activity predicts future susceptibility to seizures in mice.Nature communications · 2026Article
- Adenosine metabolic clearance maintains liver homeostasis by licensing arginine methylation of RIPK1.The Journal of experimental medicine · 2026Article
- Anti-seizure potential of J4, an equilibrative nucleoside transporter 1 inhibitor, in a mouse model of tuberous sclerosis complex in response to pentylenetetrazol.Cell & bioscience · 2026Article
- Microbiota-driven epigenetic programming of local immunity.Frontiers in immunology · 2026Review
- Fumonisin BEpigenetics · 2025Article
- Advances and challenges in experimental models of posttraumatic epilepsy for therapeutic interventions.Pharmacological reviews · 2025Review
- GLUT1 and Cerebral Glucose Hypometabolism in Human Focal Cortical Dysplasia Is Associated with Hypermethylation of Key Glucose Regulatory Genes.Molecular neurobiology · 2025Article
- Vagus Nerve Stimulation Inhibits DNA and RNA Methylation in a Rat Model of Pilocarpine-Induced Temporal Lobe Epilepsy.CNS neuroscience & therapeutics · 2025Article
- Sudden Unexpected Death in Epilepsy: A Narrative Review of Mechanism, Risks, and Prevention.Journal of clinical medicine · 2025Review
- Adenosine Kinase: An Epigenetic Modulator and Drug Target.Journal of inherited metabolic disease · 2025Review
- Adenosine transmission from hypothalamic tanycytes to AGRP/NPY neurons regulates energy homeostasis.Experimental & molecular medicine · 2025Article
- Article
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100 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Epigenetic modifications, including changes in DNA methylation, lead to altered gene expression and thus may underlie epileptogenesis via induction of permanent changes in neuronal excitability. Therapies that could inhibit or reverse these changes may be highly effective in halting disease progression. Here we identify an epigenetic function of the brain's endogenous anticonvulsant adenosine, showing that this compound induces hypomethylation of DNA via biochemical interference with the transmethylation pathway. We show that inhibition of DNA methylation inhibited epileptogenesis in multiple seizure models. Using a rat model of temporal lobe epilepsy, we identified an increase in hippocampal DNA methylation, which correlates with increased DNA methyltransferase activity, disruption of adenosine homeostasis, and spontaneous recurrent seizures. Finally, we used bioengineered silk implants to deliver a defined dose of adenosine over 10 days to the brains of epileptic rats. This transient therapeutic intervention reversed the DNA hypermethylation seen in the epileptic brain, inhibited sprouting of mossy fibers in the hippocampus, and prevented the progression of epilepsy for at least 3 months. These data demonstrate that pathological changes in DNA methylation homeostasis may underlie epileptogenesis and reversal of these epigenetic changes with adenosine augmentation therapy may halt disease progression.
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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.