ArticleGenes, brain, and behavior2010
Genetic loss of D-amino acid oxidase activity reverses schizophrenia-like phenotypes in mice.
Article in Genes, brain, and behavior, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Rational and Translational Implications of D-Amino Acids for Treatment-Resistant Schizophrenia: From Neurobiology to the Clinics.Biomolecules · 2022Pooled it
- DAAO Mutant Sites among Different Mice Strains and Their Effects on Enzyme Activity.The protein journal · 2025Article
- Cross species review of the physiological role of D-serine in translationally relevant behaviors.Amino acids · 2023Review
- Olfactory Dysfunction in Schizophrenia: Evaluating Olfactory Abilities Across Species.Current topics in behavioral neurosciences · 2023Review
- Targeting D-Amino Acid Oxidase (DAAO) for the Treatment of Schizophrenia: Rationale and Current Status of Research.CNS drugs · 2022Article
- Review
- Integrated network pharmacology and hepatic metabolomics to reveal the mechanism ofFrontiers in cell and developmental biology · 2022Article
- Converging Evidence on D-Amino Acid Oxidase-Dependent Enhancement of Hippocampal Firing Activity and Passive Avoidance Learning in Rats.The international journal of neuropsychopharmacology · 2021Article
- The Role of the N-Methyl-D-Aspartate Receptors in Social Behavior in Rodents.International journal of molecular sciences · 2019Review
- Neuronal serine racemase associates with Disrupted-In-Schizophrenia-1 and DISC1 agglomerates: Implications for schizophrenia.Neuroscience letters · 2019Article
- D-Serine: Potential Therapeutic Agent and/or Biomarker in Schizophrenia and Depression?Frontiers in psychiatry · 2019Review
- DNA methylation landscape of the genes regulating D-serine and D-aspartate metabolism in post-mortem brain from controls and subjects with schizophrenia.Scientific reports · 2018Article
- Behavioral predictors of alcohol drinking in a neurodevelopmental rat model of schizophrenia and co-occurring alcohol use disorder.Schizophrenia research · 2018Article
- Mouse d-Amino-Acid Oxidase: Distribution and Physiological Substrates.Frontiers in molecular biosciences · 2017Review
- The involvement of N-methyl-D-aspartate receptor (NMDAR) subunit NR1 in the pathophysiology of schizophrenia.Acta biochimica et biophysica Sinica · 2016Review
- In Sickness and in Health: Perineuronal Nets and Synaptic Plasticity in Psychiatric Disorders.Neural plasticity · 2016Review
- The NMDA Receptor and Schizophrenia: From Pathophysiology to Treatment.Advances in pharmacology (San Diego, Calif.) · 2016Review
- Prenatal Nicotine Exposure Impairs the Proliferation of Neuronal Progenitors, Leading to Fewer Glutamatergic Neurons in the Medial Prefrontal Cortex.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2016Article
- Insecticide imidacloprid influences cognitive functions and alters learning performance and related gene expression in a rat model.International journal of experimental pathology · 2015Article
- The NMDA receptor 'glycine modulatory site' in schizophrenia: D-serine, glycine, and beyond.Current opinion in pharmacology · 2015Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Reduced function of the N-methyl-d-aspartate receptor (NMDAR) has been implicated in the pathophysiology of schizophrenia. The NMDAR contains a glycine binding site in its NR1 subunit that may be a useful target for the treatment of schizophrenia. In this study, we assessed the therapeutic potential of long-term increases in the brain levels of the endogenous NMDAR glycine site agonist D-serine, through the genetic inactivation of its catabolic enzyme D-amino acid oxidase (DAO) in mice. The effects of eliminating DAO function were investigated in mice that display schizophrenia-related behavioral deficits due to a mutation (Grin 1(D481N)) in the NR1 subunit that results in a reduction in NMDAR glycine affinity. Grin 1(D481N) mice show deficits in sociability, prolonged latent inhibition, enhanced startle reactivity and impaired spatial memory. The hypofunctional Dao 1(G181R) mutation elevated brain levels of D-serine, but alone it did not affect performance in the behavioral measures. Compared to animals with only the Grin 1(D481N) mutation, mice with both the Dao1(G181R) and Grin 1(D481N) mutations displayed an improvement in social approach and spatial memory retention, as well as a reversal of abnormally persistent latent inhibition and a partial normalization of startle responses. Thus, an increased level of D-serine resulting from decreased catalysis corrected the performance of mice with deficient NMDAR glycine site activation in behavioral tasks relevant to the negative and cognitive symptoms of schizophrenia. Diminished DAO activity and elevations in D-serine may serve as an effective therapeutic intervention for the treatment of psychiatric symptoms.
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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.