ArticleFrontiers in cellular neuroscience2016
D-Serine and Serine Racemase Are Associated with PSD-95 and Glutamatergic Synapse Stability.
Article in Frontiers in cellular neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
What it found
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Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- Pooled it
- Synapse Pathology in Schizophrenia: A Meta-analysis of Postsynaptic Elements in Postmortem Brain Studies.Schizophrenia bulletin · 2020Pooled it
- Olfactory Three-Needle Electroacupuncture Improved Synaptic Plasticity and Gut Microbiota of SAMP8 Mice by Stimulating Olfactory Nerve.Chinese journal of integrative medicine · 2024Article
- D-serine availability modulates prefrontal cortex inhibitory interneuron development and circuit maturation.Scientific reports · 2023Article
- Reduced d-serine levels drive enhanced non-ionotropic NMDA receptor signaling and destabilization of dendritic spines in a mouse model for studying schizophrenia.Neurobiology of disease · 2022Article
- Article
- Human Serine Racemase Weakly Binds the Third PDZ Domain of PSD-95.International journal of molecular sciences · 2022Article
- Serine Racemase Expression by Striatal Neurons.Cellular and molecular neurobiology · 2022Article
- Increased excitation-inhibition balance and loss of GABAergic synapses in the serine racemase knockout model of NMDA receptor hypofunction.Journal of neurophysiology · 2021Article
- Forebrain expression of serine racemase during postnatal development.Neurochemistry international · 2021Article
- Absence of RNA-binding protein FXR2P prevents prolonged phase of kainate-induced seizures.EMBO reports · 2021Article
- Racemization in Post-Translational Modifications Relevance to Protein Aging, Aggregation and Neurodegeneration: Tip of the Iceberg.Symmetry · 2021Article
- Postsynaptic Serine Racemase Regulates NMDA Receptor Function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- D-Serine Signaling and NMDAR-Mediated Synaptic Plasticity Are Regulated by System A-Type of Glutamine/D-Serine Dual Transporters.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- D-Serine as the gatekeeper of NMDA receptor activity: implications for the pharmacologic management of anxiety disorders.Translational psychiatry · 2020Review
- D-Serine, the Shape-Shifting NMDA Receptor Co-agonist.Neurochemical research · 2020Review
- The origin of NMDA receptor hypofunction in schizophrenia.Pharmacology & therapeutics · 2020Review
- The NMDA receptor activation by d-serine and glycine is controlled by an astrocytic Phgdh-dependent serine shuttle.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Neurotoxic astrocytes express the d-serine synthesizing enzyme, serine racemase, in Alzheimer's disease.Neurobiology of disease · 2019Article
- Application and prospects of butylphthalide for the treatment of neurologic diseases.Chinese medical journal · 2019Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
D-serine is an endogenous coagonist at the glycine site of synaptic NMDA receptors (NMDARs), synthesized by serine racemase (SR) through conversion of L-serine. It is crucial for synaptic plasticity and is implicated in schizophrenia. Our previous studies demonstrated specific loss of SR, D-serine-responsive synaptic NMDARs, and glutamatergic synapses in cortical neurons lacking α7 nicotinic acetylcholine receptors, which promotes glutamatergic synapse formation and maturation during development. We thus hypothesize that D-serine and SR (D-serine/SR) are associated with glutamatergic synaptic development. Using morphological and molecular studies in cortical neuronal cultures, we demonstrate that D-serine/SR are associated with PSD-95 and NMDARs in postsynaptic neurons and with glutamatergic synapse stability during synaptic development. Endogenous D-serine and SR colocalize with PSD-95, but not presynaptic vesicular glutamate transporter 1 (VGLUT1), in glutamatergic synapses of cultured cortical neurons. Low-density astrocytes in cortical neuronal cultures lack SR expression but contain enriched D-serine in large vesicle-like structures, suggesting possible synthesis of D-serine in postsynaptic neurons and storage in astrocytes. More interestingly, endogenous D-serine and SR colocalize with PSD-95 in the postsynaptic terminals of glutamatergic synapses during early and late synaptic development, implicating involvement of D-serine/SR in glutamatergic synaptic development. Exogenous application of D-serine enhances the interactions of SR with PSD-95 and NR1, and increases the number of VGLUT1- and PSD-95-positive glutamatergic synapses, suggesting that exogenous D-serine enhances postsynaptic SR/PSD-95 signaling and stabilizes glutamatergic synapses during cortical synaptic development. This is blocked by NMDAR antagonist 2-amino-5-phosphonopentanoic acid (AP5) and 7-chlorokynurenic acid (7-CK), a specific antagonist at the glycine site of NMDARs, demonstrating that D-serine effects are mediated through postsynaptic NMDARs. Conversely, exogenous application of glycine has no such effects, suggesting D-serine, rather than glycine, modulates postsynaptic events. Taken together, our findings demonstrate that D-serine/SR are associated with PSD-95 and NMDARs in postsynaptic neurons and with glutamatergic synapse stability during synaptic development, implicating D-serine/SR as regulators of cortical synaptic and circuit development.
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