ArticleTranslational psychiatry2015
A role for D-aspartate oxidase in schizophrenia and in schizophrenia-related symptoms induced by phencyclidine in mice.
Article in Translational psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 53 citations in OpenAlex.
- Blood levels of D-aspartate oxidase, D-amino acid oxidase, serine racemase, and pLG72 are influenced by diagnoses of schizophrenia and autism spectrum disorder.Schizophrenia (Heidelberg, Germany) · 2026Article
- Metabolic Mechanisms in Electroconvulsive Therapy for Schizophrenia: Role, Potential and Future Directions.International journal of molecular sciences · 2026Review
- Free D-aspartate modulates the expression of proteins linked to schizophrenia and autism spectrum disorder during early postnatal life.Cellular and molecular life sciences : CMLS · 2025Article
- Impact of D-Amino Acids in Schizophrenia.Biomolecules · 2025Review
- Central Neurophysiological Alterations in Dystrophic mdx Mice Correlate With Reduced Hippocampal Levels of the Endogenous NMDA Receptor Ligand D-Aspartate.Journal of neurochemistry · 2025Article
- Advanced preclinical functional magnetic resonance imaging of the brain.Npj imaging · 2025Review
- Further evidence supporting the role of GTDC1 in glycine metabolism and neurodevelopmental disorders.European journal of human genetics : EJHG · 2024Article
- Asparagine reduces the risk of schizophrenia: a bidirectional two-sample mendelian randomization study of aspartate, asparagine and schizophrenia.BMC psychiatry · 2024Article
- Decreased free D-aspartate levels in the blood serum of patients with schizophrenia.Frontiers in psychiatry · 2024Article
- On the regulation of human D-aspartate oxidase.Protein science : a publication of the Protein Society · 2023Article
- Amino acid metabolism in health and disease.Signal transduction and targeted therapy · 2023Review
- Promising applications of D-amino acids in periprosthetic joint infection.Bone research · 2023Review
- The Role of D-Serine and D-Aspartate in the Pathogenesis and Therapy of Treatment-Resistant Schizophrenia.Nutrients · 2022Review
- D-aspartate oxidase gene duplication induces social recognition memory deficit in mice and intellectual disabilities in humans.Translational psychiatry · 2022Article
- d-Amino Acids and pLG72 in Alzheimer's Disease and Schizophrenia.International journal of molecular sciences · 2021Review
- Emerging imaging methods to study whole-brain function in rodent models.Translational psychiatry · 2021Review
- The M1/M4 preferring muscarinic agonist xanomeline modulates functional connectivity and NMDAR antagonist-induced changes in the mouse brain.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Development of type I/II oligodendrocytes regulated by teneurin-4 in the murine spinal cord.Scientific reports · 2020Article
- Common functional networks in the mouse brain revealed by multi-centre resting-state fMRI analysis.NeuroImage · 2020Article
- Glycine Signaling in the Framework of Dopamine-Glutamate Interaction and Postsynaptic Density. Implications for Treatment-Resistant Schizophrenia.Frontiers in psychiatry · 2020Review
Corrections and comments
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Authors and funding
18 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increasing evidence points to a role for dysfunctional glutamate N-methyl-D-aspartate receptor (NMDAR) neurotransmission in schizophrenia. D-aspartate is an atypical amino acid that activates NMDARs through binding to the glutamate site on GluN2 subunits. D-aspartate is present in high amounts in the embryonic brain of mammals and rapidly decreases after birth, due to the activity of the enzyme D-aspartate oxidase (DDO). The agonistic activity exerted by D-aspartate on NMDARs and its neurodevelopmental occurrence make this D-amino acid a potential mediator for some of the NMDAR-related alterations observed in schizophrenia. Consistently, substantial reductions of D-aspartate and NMDA were recently observed in the postmortem prefrontal cortex of schizophrenic patients. Here we show that DDO mRNA expression is increased in prefrontal samples of schizophrenic patients, thus suggesting a plausible molecular event responsible for the D-aspartate imbalance previously described. To investigate whether altered D-aspartate levels can modulate schizophrenia-relevant circuits and behaviors, we also measured the psychotomimetic effects produced by the NMDAR antagonist, phencyclidine, in Ddo knockout mice (Ddo(-)(/-)), an animal model characterized by tonically increased D-aspartate levels since perinatal life. We show that Ddo(-/-) mice display a significant reduction in motor hyperactivity and prepulse inhibition deficit induced by phencyclidine, compared with controls. Furthermore, we reveal that increased levels of D-aspartate in Ddo(-/-) animals can significantly inhibit functional circuits activated by phencyclidine, and affect the development of cortico-hippocampal connectivity networks potentially involved in schizophrenia. Collectively, the present results suggest that altered D-aspartate levels can influence neurodevelopmental brain processes relevant to schizophrenia.
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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.