[Role of D-serine in the mammalian brain].
D-Serine has recently been identified as a major gliotransmitter in the mammal central nervous system (CNS). The distribution of D-serine is analogous to the N-methyl-D-aspartate (NMDA)-type glutamate receptors in the brain. D-Serine is as potent as glycine as a coagonist at the glycine-binding site of NMDA receptors. Thus, D-serine has been considered as an endogenous ligand of the NMDA receptors in the brain. D-Serine is synthesized by serine racemase (SR) from L-serine. Both D-serine and SR have been enriched to astrocytes which are the dynamic partners of neurons at synapses and participate in controlling synaptic transmission, synaptic plasticity and synaptogenesis. The present review highlights the most recent findings on the molecular mechanisms of controlling D-serine metabolism in the CNS, the physiological role of D-serine in synaptic plasticity, and the pathological relevance of D-serine to schizophrenia, excitotoxicity- and neuroinflammation-induced neuronal death as well as neuropathic pain. Finally, as we have recently established SR knockout mouse strain with pure C57BL/6 genetic background, this novel mouse model will contribute the analysis of physiological and pathophysiological role of D-serine in vivo.
Department of Molecular Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Zhao
Z
Ying-Luan
Ying-Luan
YL
Zhao
Hisashi
H
Mori
D000818:Animals; D001253:Astrocytes / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000502:physiology*; D016923:Cell Death; D051379:Mice; D009473:Neuronal Plasticity; D018377:Neurotransmitter Agents / Q000502:physiology; D010146:Pain / Q000209:etiology; D019998:Racemases and Epimerases / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012559:Schizophrenia / Q000209:etiology; D012694:Serine / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission; D000099300:Serine Racemase
D018377:Neurotransmitter Agents; D019998:Racemases and Epimerases; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D000099300:Serine Racemase