ArticleFrontiers in neuroscience2019
D-Serine Contributes to Seizure Development via ERK Signaling.
Article in Frontiers in neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- The Gut Microbiome in Early Ontogeny: Implications for Brain and Immune System Development.Journal of developmental biology · 2026Review
- mtDNA leakage promotes neuron-glia crosstalk to induce epilepsy by cGAS-STING-driven neuroinflammation and serine metabolic reprogramming.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- D-serine: A Multitalented Neuromodulator in Brain Function, Systemic Homeostasis, and Disease.Cellular and molecular neurobiology · 2026Review
- Cerebrospinal Fluid Neurotransmitters, Pterins, Folates and Amino Acids in Paediatric Onset Epilepsies: A Tertiary Centre Retrospective Cohort Study.Children (Basel, Switzerland) · 2025Article
- Pharmacological inhibition of PSPH reduces serine levels and epileptic seizures.Nature chemical biology · 2025Article
- Neurodevelopmental Disorders Associated with Gut Microbiome Dysbiosis in Children.Children (Basel, Switzerland) · 2024Review
- New clues for the role of cerebellum in schizophrenia and the associated cognitive impairment.Frontiers in cellular neuroscience · 2024Review
- The role of the gut-microbiome-brain axis in metabolic remodeling amongst children with cerebral palsy and epilepsy.Frontiers in neurology · 2023Article
- The Role of the Possible Receptors and Intracellular Pathways in Protective Effect of Exogenous Anandamide in Kindling Model of Epilepsy.Neurochemical research · 2022Article
- Myo-Inositol Limits Kainic Acid-Induced Epileptogenesis in Rats.International journal of molecular sciences · 2022Article
- Pathological Targets for Treating Temporal Lobe Epilepsy: Discoveries From Microscale to Macroscale.Frontiers in neurology · 2021Review
- Epilepsy in inherited neurotransmitter disorders: Spotlights on pathophysiology and clinical management.Metabolic brain disease · 2021Review
- Pharmacokinetic, pharmacodynamic, and neurochemical investigations of lamotrigine-pentylenetetrazole kindled mice to ascertain it as a reliable model for clinical drug-resistant epilepsy.Animal models and experimental medicine · 2020Article
- Astrocytes as Guardians of Neuronal Excitability: Mechanisms Underlying Epileptogenesis.Frontiers in neurology · 2020Review
- Selective demethylation of two CpG sites causes postnatal activation of the Dao gene and consequent removal of D-serine within the mouse cerebellum.Clinical epigenetics · 2019Article
- d-amino Acids in Health and Disease: A Focus on Cancer.Nutrients · 2019Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A seizure is one of the leading neurological disorders. NMDA receptor-mediated neuronal excitation has been thought to be essential for epileptogenesis. As an endogenous co-agonist of the NMDA receptor, D-serine has been suggested to play a role in epileptogenesis. However, the underlying mechanisms remain unclear. In the current study, we investigated the effects of antagonizing two key enzymes in D-serine metabolism on the development of seizures and the downstream signaling. Our results showed that serine racemase (SR), a key enzyme in regulating the L-to-D-serine conversion, was significantly up-regulated in hippocampal astrocytes in rats and patients who experienced seizure, in comparison with control rats and patients. L-aspartic acid β-hydroxamate (LaaβH), an inhibitor of SR, significantly prolonged the latencies of seizures, shortened the durations of seizures, and decreased the total EEG power in rats. In contrast, D-amino acid oxidase inhibitor 5-chlorobenzo[d]isoxazol-3-ol (CBIO), which can increase D-serine levels, showed the opposite effects. Furthermore, our data showed that LaaβH and CBIO significantly affected the phosphorylation of Extracellular Signal-regulated Kinase (ERK). Antagonizing or activating ERK could significantly block the effects of LaaβH/CBIO on the occurrence of seizures. In summary, our study revealed that D-serine is involved in the development of epileptic seizures, partially through ERK signaling, indicating that the metabolism of D-serine may be targeted for the treatment of epilepsy.
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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.