ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2016
Age-Related Changes in D-Aspartate Oxidase Promoter Methylation Control Extracellular D-Aspartate Levels and Prevent Precocious Cell Death during Brain Aging.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 76 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
- 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
- Crystal structure of D-aspartate oxidase from Cryptococcus humicola UJ1.Acta crystallographica. Section F, Structural biology communications · 2025Article
- Central Neurophysiological Alterations in Dystrophic mdx Mice Correlate With Reduced Hippocampal Levels of the Endogenous NMDA Receptor Ligand D-Aspartate.Journal of neurochemistry · 2025Article
- Aspartate in the Brain: A Review.Neurochemical research · 2025Review
- Prenatal Exposure to Lipopolysaccharide or Valproate Leads to Abnormal Accumulation of the NMDA Receptor Agonist D-Aspartate in the Adolescent Rat Brain.Journal of neurochemistry · 2025Article
- Modulating the serine metabolism in human differentiated astrocytes: an integrated multi omics approach.Frontiers in cellular neuroscience · 2025Article
- L-serine deficiency: on the properties of the Asn133Ser variant of human phosphoserine phosphatase.Scientific reports · 2024Article
- Elevated peripheral glutamate and upregulated expression of NMDA receptor NR1 subunit in insomnia disorder.Frontiers in psychiatry · 2024Article
- CHRISTMAS: Chiral Pair Isobaric Labeling Strategy for Multiplexed Absolute Quantitation of Enantiomeric Amino Acids.Analytical chemistry · 2023Article
- Changes in aspartate metabolism in the medial-prefrontal cortex of nicotine addicts based on J-edited magnetic resonance spectroscopy.Human brain mapping · 2023Article
- Article
- On the regulation of human D-aspartate oxidase.Protein science : a publication of the Protein Society · 2023Article
- Specific Methyl-CpG Configurations Define Cell Identity through Gene Expression Regulation.International journal of molecular sciences · 2023Article
- Biomarkers of Activity-Dependent Plasticity and Persistent Enhancement of Synaptic Transmission in Alzheimer Disease: A Review of the Current Status.Medical science monitor : international medical journal of experimental and clinical research · 2023Review
- D-aspartate oxidase gene duplication induces social recognition memory deficit in mice and intellectual disabilities in humans.Translational psychiatry · 2022Article
- 2-Pentadecyl-2-oxazoline ameliorates memory impairment and depression-like behaviour in neuropathic mice: possible role of adrenergic alpha2- and H3 histamine autoreceptors.Molecular brain · 2021Article
- Serum D-serine levels are altered in early phases of Alzheimer's disease: towards a precocious biomarker.Translational psychiatry · 2021Article
- Simultaneous Measurement of Amino Acid Enantiomers in Aged Mouse Brain Samples by LC/MS/MS Combined with Derivatization UsingMetabolites · 2021Article
- Human D-aspartate Oxidase: A Key Player in D-aspartate Metabolism.Frontiers in molecular biosciences · 2021Article
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Authors and funding
20 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The endogenous NMDA receptor (NMDAR) agonist D-aspartate occurs transiently in the mammalian brain because it is abundant during embryonic and perinatal phases before drastically decreasing during adulthood. It is well established that postnatal reduction of cerebral D-aspartate levels is due to the concomitant onset of D-aspartate oxidase (DDO) activity, a flavoenzyme that selectively degrades bicarboxylic D-amino acids. In the present work, we show that d-aspartate content in the mouse brain drastically decreases after birth, whereas Ddo mRNA levels concomitantly increase. Interestingly, postnatal Ddo gene expression is paralleled by progressive demethylation within its putative promoter region. Consistent with an epigenetic control on Ddo expression, treatment with the DNA-demethylating agent, azacitidine, causes increased mRNA levels in embryonic cortical neurons. To indirectly evaluate the effect of a putative persistent Ddo gene hypermethylation in the brain, we used Ddo knock-out mice (Ddo(-/-)), which show constitutively suppressed Ddo expression. In these mice, we found for the first time substantially increased extracellular content of d-aspartate in the brain. In line with detrimental effects produced by NMDAR overstimulation, persistent elevation of D-aspartate levels in Ddo(-/-) brains is associated with appearance of dystrophic microglia, precocious caspase-3 activation, and cell death in cortical pyramidal neurons and dopaminergic neurons of the substantia nigra pars compacta. This evidence, along with the early accumulation of lipufuscin granules in Ddo(-/-) brains, highlights an unexpected importance of Ddo demethylation in preventing neurodegenerative processes produced by nonphysiological extracellular levels of free D-aspartate.
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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.