Cited by 415Neuroscience and Neuropharmacology ResearchAmino Acid Enzymes and MetabolismNeuroinflammation and Neurodegeneration Mechanisms

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d-Serine as a Neuromodulator: Regional and Developmental Localizations in Rat Brain Glia Resemble NMDA Receptors

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Schell, Michael J., Brady Jr., Roscoe O., Molliver, Mark E., Snyder, Solomon H.·1997·The Journal of Neuroscience

DOI 10.1523/jneurosci.17-05-01604.1997PMC PMC6573391

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Abstract

d-Serine is localized in mammalian brain to a discrete population of glial cells near NMDA receptors, suggesting that d-serine is an endogenous agonist of the receptor-associated glycine site. To explore this possibility, we have compared the immunohistochemical localizations of d-serine, glycine, and NMDA receptors in rat brain. In the telencephalon,d-serine is concentrated in protoplasmic astrocytes, which are abundant in neuropil in close vicinity to NMDA receptor 2A/B subunits. Ultrastructural examination of the CA1 region of hippocampus reveals d-serine in the cytosolic matrix of astrocytes that ensheath neurons and blood vessels, whereas NR2A/B is concentrated in dendritic spines. By contrast, glycine immunoreactivity in telencephalon is the lowest in brain. During postnatal week 2,d-serine levels in cerebellum are comparable to those in adult cerebral cortex but fall to undetectable levels by day 26. During week 2, we observe parallel ontogeny of d-serine in Bergmann glia and NR2A/B in Purkinje cells, suggesting a role for astrocytic d-serine in NMDA receptor-mediated synaptogenesis.d-Serine in the radial processes of Bergmann glia is also well positioned to regulate NMDA receptor-dependent granule cell migration. In the inner granule layer,d-serine is found transiently in protoplasmic astrocytes surrounding glomeruli, where it could regulate development of the mossy fiber/granule cell synapse.d-Serine seems to be the endogenous ligand of glycine sites in the telencephalon and developing cerebellum, whereas glycine predominates in the adult cerebellum, olfactory bulb, and hindbrain.

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Authors: Schell, M. J., Brady Jr., R. O., Molliver, M. E., & Snyder, S. H.
Affiliations: Johns Hopkins University (US)
ORCID: Schell, Michael J.
Snyder, Solomon H.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 1997-03-01
Volume: 17
Issue: 5
Pages: 1604-1615
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.17-05-01604.1997
PMC: PMC6573391
OpenAlex: W1793612468
Cited by: 415
References: 80
Citations by year: 2026: 1 · 2025: 6 · 2024: 8 · 2023: 13 · 2022: 11 · 2021: 14 · 2020: 12 · 2019: 12 · 2018: 12 · 2017: 8 · 2016: 14 · 2015: 12 · 2014: 18 · 2013: 17 · 2012: 15
FWCI: 4.46
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 184 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01da004431-08)
U.S. Public Health Service
National Institute of Mental Health (R01MH018501, R37MH018501, MH-18501)
National Institute on Drug Abuse (DA 00074, 5RO1DA04431, K05DA000074)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: D-serine, NMDA receptor, glycine site, neuromodulation, astrocytes, Bergmann glia, glycine, cerebellar development, hippocampal CA1, synaptogenesis, granule cell migration, mossy fiber synapses, telencephalon, postnatal development, rat brain
MeSH terms: Animals, Brain Chemistry, Cerebellum, Glycine, Hippocampus, Ligands, Models, Neurological, Neuroglia, Olfactory Bulb, Organ Specificity, Rabbits, Rhombencephalon, Serine, Stereoisomerism, Telencephalon, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Receptors, Glycine, Neurotransmitter Agents, Rats

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d-Serine as a Neuromodulator: Regional and Developmental Localizations in Rat Brain Glia Resemble NMDA Receptors

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