title: D-serine as a neuromodulator: regional and developmental localizations in rat brain glia resemble NMDA receptors.
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.
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Schell
authors.forename: R O
authors.initials: RO
authors.lastname: Brady
authors.forename: M E
authors.initials: ME
authors.lastname: Molliver
authors.forename: S H
authors.initials: SH
authors.lastname: Snyder
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D002531:Cerebellum / Q000378:metabolism / Q000648:ultrastructure; D005998:Glycine / Q000032:analysis; D006624:Hippocampus / Q000378:metabolism / Q000648:ultrastructure; D008024:Ligands; D008959:Models, Neurological; D009457:Neuroglia / Q000378:metabolism* / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000032:analysis / Q000502:physiology*; D009830:Olfactory Bulb / Q000378:metabolism / Q000648:ultrastructure; D009928:Organ Specificity; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D018009:Receptors, Glycine / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate; D012249:Rhombencephalon / Q000378:metabolism / Q000648:ultrastructure; D012694:Serine / Q000032:analysis / Q000502:physiology*; D013237:Stereoisomerism; D013687:Telencephalon / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D008024:Ligands; D018377:Neurotransmitter Agents; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D005998:Glycine