Immunocytochemical analysis of D-serine distribution in the mammalian brain reveals novel anatomical compartmentalizations in glia and neurons

• Published in: Glia Vol. 53; no. 4; pp. 401 - 411
• Main Authors: Williams, Susan M., Diaz, Claudia M., Macnab, Lauren T., Sullivan, Robert K.P., Pow, David V.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01-03-2006; Wiley-Liss
• Subjects: Aging - metabolism; Animals; astrocyte; Biological and medical sciences; Biomarkers; Brain - cytology; Brain Chemistry - physiology; Fixatives; Formaldehyde; Fundamental and applied biological sciences. Psychology; gamma-Aminobutyric Acid - metabolism; Glial Fibrillary Acidic Protein - metabolism; Glutamic Acid - metabolism; glycine; Glycine - metabolism; Immunohistochemistry; Isolated neuron and nerve. Neuroglia; microglia; Microscopy, Electron; Neuroglia - metabolism; Neurons - metabolism; Neurotransmitter Agents - metabolism; NMDA; Rats; Rats, Wistar; Receptors, Glutamate - metabolism; Serine - metabolism; Synaptic Vesicles - metabolism; Synaptic Vesicles - ultrastructure; Tissue Fixation; Vertebrates: nervous system and sense organs; vesicle; Compartmentalization; Glial cell; Immunocytochemistry; Neuroglia; Serine; Central nervous system; vesicle; Astrocyte; Glycine; Encephalon; Microglia; Vertebrata; Mammalia; Neuron; Distribution; NMDA
• ISSN: 0894-1491; 1098-1136
• DOI: 10.1002/glia.20300

D‐Serine is a co‐agonist at the NMDA receptor glycine‐binding site. Early studies have emphasized a glial localization for D‐serine. However the nature of the glial cells has not been fully resolved, because previous D‐serine antibodies needed glutaraldehyde‐fixation, precluding co‐localization with fixation‐sensitive antigens. We have raised a new D‐serine antibody optimized for formaldehyde‐fixation. Light and electron microscopic observations indicated that D‐serine was concentrated into vesicle‐like compartments in astrocytes and radial glial cells, rather than being distributed uniformly in the cytoplasm. In aged animals, patches of cortex and hippocampus were devoid of immunolabeling for D‐serine, suggesting that impaired glial modulation of forebrain glutamatergic signaling might occur. Dual immunofluorescence labeling for glutamate and D‐serine revealed D‐serine in a subset of glutamatergic neurons, particularly in brainstem regions and in the olfactory bulbs. Microglia also contain D‐serine. We suggest that some D‐serine may be derived from the periphery. Collectively, our data suggest that the cellular compartmentation and distribution of D‐serine may be more complex and extensive than previously thought and may have significant implications for our understanding of the role of D‐serine in disease states including hypoxia and schizophrenia. © 2005 Wiley‐Liss, Inc.