ArticleFrontiers in molecular neuroscience2020
Sarcosine Suppresses Epileptogenesis in Rats With Effects on Hippocampal DNA Methylation.
Article in Frontiers in molecular neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Sarcosine Remodels DNA Methylation-Linked Transcriptional Networks During Epileptogenesis in the Rat Rapid Hippocampal Kindling Model.International journal of molecular sciences · 2026Article
- GlyT1 (SLC6A9) inhibition in neurological and psychiatric disorders.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- A model of new-onset refractory status epilepticus (NORSE) using intrahippocampal kainic acid in adolescent mice.Epilepsy research · 2026Article
- Vagus Nerve Stimulation Inhibits DNA and RNA Methylation in a Rat Model of Pilocarpine-Induced Temporal Lobe Epilepsy.CNS neuroscience & therapeutics · 2025Article
- Effect of SSR504734, a Selective Glycine Transporter Type 1 Inhibitor, on Seizure Thresholds, Neurotransmitter Levels, and Inflammatory Markers in Mice.ACS chemical neuroscience · 2025Article
- Integrated Mendelian Randomization and Single-Cell Transcriptomics Analysis Identifies Critical Blood Biomarkers and Potential Mechanisms in Epilepsy.CNS neuroscience & therapeutics · 2025Article
- Alterations in DNA 5-hydroxymethylation patterns in the hippocampus of an experimental model of chronic epilepsy.Neurobiology of disease · 2024Article
- Aerobic exercise alters DNA hydroxymethylation levels in an experimental rodent model of temporal lobe epilepsy.Epilepsy & behavior reports · 2024Article
- Multi-omic strategies applied to the study of pharmacoresistance in mesial temporal lobe epilepsy.Epilepsia open · 2022Review
- Article
- Cytosolic serine hydroxymethyltransferase controls lung adenocarcinoma cells migratory ability by modulating AMP kinase activity.Cell death & disease · 2020Article
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9 authors at 1 institution in 1 country.
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Abstract
Epileptogenesis is a common consequence of brain insults, however, the prevention or delay of the epileptogenic process remains an important unmet medical challenge. Overexpression of glycine transporter 1 (GlyT1) is proposed as a pathological hallmark in the hippocampus of patients with temporal lobe epilepsy (TLE), and we previously demonstrated in rodent epilepsy models that augmentation of glycine suppressed chronic seizures and altered acute seizure thresholds. In the present study we evaluated the effect of the GlyT1 inhibitor, sarcosine (aka N-methylglycine), on epileptogenesis and also investigated possible mechanisms. We developed a modified rapid kindling model of epileptogenesis in rats combined with seizure score monitoring to evaluate the antiepileptogenic effect of sarcosine. We used immunohistochemistry and Western blot analysis for the evaluation of GlyT1 expression and epigenetic changes of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in the epileptogenic hippocampi of rats, and further evaluated expression changes in enzymes involved in the regulation of DNA methylation, ten-eleven translocation methylcytosine dioxygenase 1 (TET1), DNA-methyltransferase 1 (DNMT1), and DNMT3a. Our results demonstrated: (i) experimental evidence that sarcosine (3 g/kg, i.p. daily) suppressed kindling epileptogenesis in rats; (ii) the sarcosine-induced antiepileptogenic effect was accompanied by a suppressed hippocampal GlyT1 expression as well as a reduction of hippocampal 5mC levels and a corresponding increase in 5hmC; and (iii) sarcosine treatment caused differential expression changes of TET1 and DNMTs. Together, these findings suggest that sarcosine has unprecedented disease-modifying properties in a kindling model of epileptogenesis in rats, which was associated with altered hippocampal DNA methylation. Thus, manipulation of the glycine system is a potential therapeutic approach to attenuate the development of epilepsy.
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