Cited by 90Neuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration MechanismsAmino Acid Enzymes and Metabolism

Potentiation of the NMDA receptor‐mediated responses through the activation of the glycine site by microglia secreting soluble factors

Hayashi, Yoshinori, Ishibashi, Hitoshi, Hashimoto, Kenji, Nakanishi, Hiroshi·2006·Glia

Abstract

We have previously reported that both transferred microglia and microglia‐conditioned medium (MCM) potentiated the N‐methyl‐D‐aspatate (NMDA) receptor‐mediated synaptic responses in cortical neurons. To elucidate the mechanism underlying the potentiation of NMDA receptor‐mediated responses by microglia, we examined the effects of MCM on NMDA‐induced inward currents in mechanically dissociated hippocampal CA1 neurons under whole‐cell patch recordings. MCM potentiated the amplitude of NMDA‐induced currents up to 10‐fold in a dose‐dependent manner, and this effect of MCM remained even after boiling or cutting off molecules with a molecular mass more than 3 kDa. In the presence of glycine with a concentration sufficient to saturate the NMDA receptor glycine site, MCM failed to further potentiate the NMDA‐induced currents. The glycine site antagonist 5, 7‐dichrolokynurenic acid, significantly inhibited the effects of MCM. The effect of MCM was still observed even after treatment with D‐amino acid oxidase, a D‐serine degrading enzyme. On the other hand, MCM had no significant effect on the voltage‐dependent Mg 2+ blockade of NMDA receptors. Furthermore, MCM enhanced the formation of the long‐term potentiation in the Schaffer collateral pathway‐CA1 pyramidal cell synapses. Using a high performance liquid chromatography system, we found the levels of both glycine and L‐serine in MCM to be significantly higher than those in the control medium. It was also noted that an increased glycine productivity of microglia was observed in the hippocampus in the acute phase of neuronal injury. These observations strongly suggest that glycine is a major causative molecule released from microglia that potentiates the NMDA‐induced currents. © 2006 Wiley‐Liss, Inc.

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Crossref · 10.1002/glia.20322

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Authors
Hayashi, Y., Ishibashi, H., Hashimoto, K., & Nakanishi, H.
Affiliations
  • Kyushu University (JP)
  • Center for Forensic Mental Health, Chiba University (JP)
Corresponding author
Nakanishi, Hiroshi
Venue
Glia
Publisher
Wiley
Published
2006-02-15
Volume
53
Issue
6
Pages
660-668
ISSN
  • 0894-1491 (ISSN-L)
  • 1098-1136
OpenAlex
W2110237840
Cited by
90
References
42
Citations by year
2026: 1 · 2025: 4 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 2 · 2019: 3 · 2018: 9 · 2017: 8 · 2016: 10 · 2015: 7 · 2014: 7 · 2013: 8 · 2012: 3
FWCI
1.39
Type
journal article
Language
en
Open access
closed
Locations
  • Glia (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Keywords
NMDA receptor potentiation, microglia, glycine site, glycine, L-serine, D-amino acid oxidase, long-term potentiation, Schaffer collateral-CA1 synapses, CA1 pyramidal neurons, neuronal injury
MeSH terms
Animals, Animals, Newborn, Cell Communication, Cells, Cultured, Dose-Response Relationship, Drug, Glycine, Hippocampus, Mice, Inbred C57BL, Synaptic Transmission, Serine, Receptors, N-Methyl-D-Aspartate, N-Methylaspartate, Culture Media, Conditioned, Rats, Wistar, Microglia, Long-Term Potentiation, Pyramidal Cells, Receptors, Glycine, Patch-Clamp Techniques, Excitatory Amino Acid Agonists, Excitatory Amino Acid Antagonists, Glutamic Acid, Mice, Rats

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