Immunocytochemical analysis of D-serine distribution in the mammalian brain reveals novel anatomical compartmentalizations in glia and neurons.
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.
Williams
Susan M
SM
Department of Anatomy, School of Biomedical Sciences, University of Newcastle, Callaghan, New South Wales 2308, Australia.
Diaz
Claudia M
CM
Macnab
Lauren T
LT
Sullivan
Robert K P
RK
Pow
David V
DV
D000375:Aging / Q000378:metabolism; D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000166:cytology*; D001923:Brain Chemistry / Q000502:physiology*; D005404:Fixatives; D005557:Formaldehyde; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000378:metabolism; D012694:Serine / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism / Q000648:ultrastructure; D016707:Tissue Fixation; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D015415:Biomarkers; D005404:Fixatives; D005904:Glial Fibrillary Acidic Protein; D018377:Neurotransmitter Agents; D017470:Receptors, Glutamate; D005557:Formaldehyde; D018698:Glutamic Acid; D012694:Serine; D005680:gamma-Aminobutyric Acid; D005998:Glycine