ArticleScientific reports2017
Olanzapine, but not clozapine, increases glutamate release in the prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase activity.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Rational and Translational Implications of D-Amino Acids for Treatment-Resistant Schizophrenia: From Neurobiology to the Clinics.Biomolecules · 2022Pooled it
- 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
- WSSV-induced reversal of the malate-aspartate shuttle facilitates viral replication in shrimp hemocytes.Cell communication and signaling : CCS · 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
- d-amino acids: new functional insights.The FEBS journal · 2025Review
- BioWalk-MDA: a novel approach for large-scale predicting metabolite-drug associations based on multi layered biomedical knowledge graphs.Briefings in bioinformatics · 2025Article
- Predicting performance in attention by measuring key metabolites in the PCC with 7T MRS.Scientific reports · 2024Article
- Interactions Involving Glycine and Other Amino Acid Neurotransmitters: Focus on Transporter-Mediated Regulation of Release and Glycine-Glutamate Crosstalk.Biomedicines · 2024Review
- Metabolomic and immune alterations in long COVID patients with chronic fatigue syndrome.Frontiers in immunology · 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
- Schizophrenia Synaptic Pathology and Antipsychotic Treatment in the Framework of Oxidative and Mitochondrial Dysfunction: Translational Highlights for the Clinics and Treatment.Antioxidants (Basel, Switzerland) · 2023Review
- The Role of D-Serine and D-Aspartate in the Pathogenesis and Therapy of Treatment-Resistant Schizophrenia.Nutrients · 2022Review
- Efficacy of Olanzapine in Anxiety Dimension of Schizophrenia: A Systematic Review of Randomized Controlled Trials.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2022Review
- Vesicle trafficking and vesicle fusion: mechanisms, biological functions, and their implications for potential disease therapy.Molecular biomedicine · 2022Review
- D-aspartate oxidase gene duplication induces social recognition memory deficit in mice and intellectual disabilities in humans.Translational psychiatry · 2022Article
- D-Aspartate consumption selectively promotes intermediate-term spatial memory and the expression of hippocampal NMDA receptor subunits.Scientific reports · 2021Article
- Human D-aspartate Oxidase: A Key Player in D-aspartate Metabolism.Frontiers in molecular biosciences · 2021Article
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
D-aspartate levels in the brain are regulated by the catabolic enzyme D-aspartate oxidase (DDO). D-aspartate activates NMDA receptors, and influences brain connectivity and behaviors relevant to schizophrenia in animal models. In addition, recent evidence reported a significant reduction of D-aspartate levels in the post-mortem brain of schizophrenia-affected patients, associated to higher DDO activity. In the present work, microdialysis experiments in freely moving mice revealed that exogenously administered D-aspartate efficiently cross the blood brain barrier and stimulates L-glutamate efflux in the prefrontal cortex (PFC). Consistently, D-aspartate was able to evoke L-glutamate release in a preparation of cortical synaptosomes through presynaptic stimulation of NMDA, mGlu5 and AMPA/kainate receptors. In support of a potential therapeutic relevance of D-aspartate metabolism in schizophrenia, in vitro enzymatic assays revealed that the second-generation antipsychotic olanzapine, differently to clozapine, chlorpromazine, haloperidol, bupropion, fluoxetine and amitriptyline, inhibits the human DDO activity. In line with in vitro evidence, chronic systemic administration of olanzapine induces a significant extracellular release of D-aspartate and L-glutamate in the PFC of freely moving mice, which is suppressed in Ddo knockout animals. These results suggest that the second-generation antipsychotic olanzapine, through the inhibition of DDO activity, increases L-glutamate release in the PFC of treated mice.
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