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

• Published in: The Journal of neuroscience 1997-03, Vol.17 (5), p.1604-1615
• Main Authors: Schell, Michael J, Brady Jr., Roscoe O, Molliver, Mark E, Snyder, Solomon H
• Format: Article
• Language: English
• Subjects: Animals; Brain Chemistry; Cerebellum - metabolism; Cerebellum - ultrastructure; Glycine - analysis; Hippocampus - metabolism; Hippocampus - ultrastructure; Ligands; Models, Neurological; Neuroglia - metabolism; Neuroglia - ultrastructure; Neurotransmitter Agents - analysis; Neurotransmitter Agents - physiology; Olfactory Bulb - metabolism; Olfactory Bulb - ultrastructure; Organ Specificity; Rabbits; Rats; Rats, Sprague-Dawley; Receptors, Glycine - metabolism; Receptors, N-Methyl-D-Aspartate; Rhombencephalon - metabolism; Rhombencephalon - ultrastructure; Serine - analysis; Serine - physiology; Stereoisomerism; Telencephalon - metabolism; Telencephalon - ultrastructure
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.17-05-01604.1997

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.