ArticleProceedings of the National Academy of Sciences of the United States of America2013
Multiple risk pathways for schizophrenia converge in serine racemase knockout mice, a mouse model of NMDA receptor hypofunction.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.
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Who cites it
135 citing papers in PubMed, 213 citations in OpenAlex.
- NYX-2925, A Novel N-methyl-D-aspartate Receptor Modulator: A First-in-Human, Randomized, Double-blind Study of Safety and Pharmacokinetics in Adults.Clinical and translational science · 2019Trial
- Adolescent Exposure to a THC-Rich Cannabis Extract Produces Genotype-Dependent Effects on Cognition and Glial Morphology in Serine Racemase Mutant Mice.Journal of neurochemistry · 2026Article
- Glycine decarboxylase as a novel regulator of N-methyl-D-aspartate receptor function: Implications for pathophysiology of schizophrenia.Neural regeneration research · 2026Article
- Biomolecular and cellular chirality: Novel diagnostic perspectives for diseases.APL bioengineering · 2026Review
- Novel drug treatments for schizophrenia.Nature reviews. Drug discovery · 2026Review
- Review
- GRIN2A null variants confer a high risk for early-onset schizophrenia and other mental disorders and potentially enable precision therapy.Molecular psychiatry · 2026Article
- Glycine Reverses Behavioral Deficits in a Mouse Model for Psychosis With 4 Copies of the Gldc Gene.Pharmacology research & perspectives · 2025Article
- Impact of D-Amino Acids in Schizophrenia.Biomolecules · 2025Review
- An increased copy number of glycine decarboxylase (GLDC) associated with psychosis reduces extracellular glycine and impairs NMDA receptor function.Molecular psychiatry · 2025Article
- D-Serine May Ameliorate Hippocampal Synaptic Plasticity Impairment Induced by Patients' Anti-N-methyl-D-aspartate Receptor Antibodies in Mice.Biomedicines · 2024Article
- Advances and challenges in serine in the central nervous system: physicochemistry, physiology, and pharmacology.Metabolic brain disease · 2024Review
- Impact of Serine Racemase Deletion on Nicotine Discrimination.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2024Article
- Dysfunction of the NMDA Receptor in the Pathophysiology of Schizophrenia and/or the Pathomechanisms of Treatment-Resistant Schizophrenia.Biomolecules · 2024Review
- Chemical Probes to Investigate Central Nervous System Disorders: Design, Synthesis and Mechanism of Action of a Potent Human Serine Racemase Inhibitor.ACS medicinal chemistry letters · 2024Article
- Neurostructural subgroup in 4291 individuals with schizophrenia identified using the subtype and stage inference algorithm.Nature communications · 2024Article
- Longitudinal trajectories of anterior cingulate glutamate and subclinical psychotic experiences in early adolescence: the impact of bullying victimization.Molecular psychiatry · 2024Article
- Decreased free D-aspartate levels in the blood serum of patients with schizophrenia.Frontiers in psychiatry · 2024Article
- Serine racemase deletion alters adolescent social behavior and whole-brain cFos activation.Frontiers in psychiatry · 2024Article
- Neurostructural changes in schizophrenia and treatment-resistance: a narrative review.Psychoradiology · 2024Review
75 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Schizophrenia is characterized by reduced hippocampal volume, decreased dendritic spine density, altered neuroplasticity signaling pathways, and cognitive deficits associated with impaired hippocampal function. We sought to determine whether this diverse pathology could be linked to NMDA receptor (NMDAR) hypofunction, and thus used the serine racemase-null mutant mouse (SR(-/-)), which has less than 10% of normal brain D-serine, an NMDAR coagonist. We found that D-serine was necessary for the maintenance of long-term potentiation in the adult hippocampal dentate gyrus and for full NMDAR activity on granule cells. SR(-/-) mice had reduced dendritic spines and hippocampal volume. These morphological changes were paralleled by diminished BDNF/Akt/mammalian target of rapamycin (mTOR) signaling and impaired performance on a trace-conditioning memory task. Chronic D-serine treatment normalized the electrophysiological, neurochemical, and cognitive deficits in SR(-/-) mice. These results demonstrate that NMDAR hypofunction can reproduce the numerous hippocampal deficits associated with schizophrenia, which can be reversed by chronic peripheral D-serine treatment.
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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.