ArticleCellular and molecular neurobiology2012
Cell selective conditional null mutations of serine racemase demonstrate a predominate localization in cortical glutamatergic neurons.
Article in Cellular and molecular neurobiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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79 citing papers in PubMed, 146 citations in OpenAlex.
- Cognitive loss after brain trauma results from sex-specific activation of synaptic pruning processes.Brain : a journal of neurology · 2026Article
- D-Serine's Journey Between Stars and Synapses.Neurochemical research · 2025Review
- SLC1A4 and Serine Homeostasis: Implications for Neurodevelopmental and Neurodegenerative Disorders.International journal of molecular sciences · 2025Review
- The Development of a Regulator of Human Serine Racemase for N-Methyl-D-aspartate Function.Biomedicines · 2024Article
- Serine racemase deletion alters adolescent social behavior and whole-brain cFos activation.Frontiers in psychiatry · 2024Article
- Cross species review of the physiological role of D-serine in translationally relevant behaviors.Amino acids · 2023Review
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- Hypothalamic Menin regulates systemic aging and cognitive decline.PLoS biology · 2023Article
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- A role for endothelial NMDA receptors in the pathophysiology of schizophrenia.Schizophrenia research · 2022Review
- Effects of Quinolinate-Induced Lesion of the Medial Prefrontal Cortex on Prefrontal and Striatal Concentrations of D-Serine in the Rat.Neurochemical research · 2022Article
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- Advances in Traumatic Brain Injury Biomarkers.Cureus · 2022Review
- Stachyose Alleviates Corticosterone-Induced Long-Term Potentiation ImpairmentFrontiers in pharmacology · 2022Article
- Serine Racemase Expression by Striatal Neurons.Cellular and molecular neurobiology · 2022Article
- Detection of Morphological Abnormalities in Schizophrenia: An Important Step to Identify Associated Genetic Disorders or Etiologic Subtypes.International journal of molecular sciences · 2021Review
- Astrocytes and Behavior.Annual review of neuroscience · 2021Article
- NMDARs, Coincidence Detectors of Astrocytic and Neuronal Activities.International journal of molecular sciences · 2021Review
- Increased excitation-inhibition balance and loss of GABAergic synapses in the serine racemase knockout model of NMDA receptor hypofunction.Journal of neurophysiology · 2021Article
19 more citing papers are in PubMed but not listed here.
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5 authors at 1 institution in 1 country.
Funding
Abstract
D-serine, which is synthesized by the enzyme serine racemase (SR), is a co-agonist at the N-methyl-D-aspartate receptor (NMDAR). Crucial to an understanding of the signaling functions of D-serine is defining the sites responsible for its synthesis and release. In order to quantify the contributions of astrocytes and neurons to SR and D-serine localization, we used recombinant DNA techniques to effect cell type selective suppression of SR expression in astrocytes (aSRCKO) and in forebrain glutamatergic neurons (nSRCKO). The majority of SR is expressed in neurons: SR expression was reduced by ~65% in nSRCKO cerebral cortex and hippocampus, but only ~15% in aSRCKO as quantified by western blots. In contrast, nSRCKO is associated with only modest decreases in D-serine levels as quantified by HPLC, whereas D-serine levels were unaffected in aSRCKO mice. Liver expression of SR was increased by 35% in the nSRCKO, suggesting a role for peripheral SR in the maintenance of brain D-serine. Electrophysiologic studies of long-term potentiation (LTP) at the Schaffer collateral-CA1 pyramidal neuron synapse revealed no alterations in the aSRCKO mice versus wild-type. LTP induced by a single tetanic stimulus was reduced by nearly 70% in the nSRCKO mice. Furthermore, the mini-excitatory post-synaptic currents mediated by NMDA receptors but not by AMPA receptors were significantly reduced in nSRCKO mice. Our findings indicate that in forebrain, where D-serine appears to be the endogenous co-agonist at NMDA receptors, SR is predominantly expressed in glutamatergic neurons, and co-release of glutamate and D-serine is required for optimal activation of post-synaptic NMDA receptors.
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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.