Abstract
Accumulating evidence during the last decade established that D-serine is a key signaling molecule utilized by neurons and astroglia in the mammalian central nervous system. D-serine is increasingly appreciated as the main physiological endogenous coagonist for synaptic NMDA receptors at central excitatory synapses; it is mandatory for long-term changes in synaptic strength, memory, learning, and social interactions. Alterations in the extracellular levels of D-serine leading to disrupted cell-cell signaling are a trademark of many chronic or acute neurological (i.e., Alzheimer disease, epilepsy, stroke) and psychiatric (i.e., schizophrenia) disorders, and are associated with addictive behavior (i.e., cocaine addiction). Indeed, fine tuning of the extracellular levels of D-serine, achieved by various molecular machineries and signaling pathways, is necessary for maintenance of accurate NMDA receptor functions. Here, we review the experimental data supporting the notion that astroglia and neurons use different pathways to regulate levels of extracellular D-serine.
Highlights
N -methyl D-aspartate receptors (NMDARs) are glutamate-gated ionotropic receptors/channels that are central to many physiological processes including learning and memory, and are involved in neurotoxicity and psychiatric disorders (Traynelis et al, 2010; Paoletti et al, 2013)
Many studies during the last 15 years have shown that D-serine, an unusual amino acid synthesized in the brain by serine racemase (SR; Campanini et al, 2013) and degraded by the peroxysomal flavoprotein D-amino acid oxidase (DAAO; Sacchi et al, 2012), is the main coagonist of synaptic NMDARs in various brain areas (Martineau et al, 2006; Wolosker, 2011; Billard, 2012; Van Horn et al, 2013)
As excellent reviews have been recently published on the biochemistry of SR (Campanini et al, 2013) and DAAO (Sacchi et al, 2012), the present review focuses primarily on the molecular entities used by neurons and astrocytes in regulation of D-serine functions
Summary
N -methyl D-aspartate receptors (NMDARs) are glutamate-gated ionotropic receptors/channels that are central to many physiological processes including learning and memory, and are involved in neurotoxicity and psychiatric disorders (Traynelis et al, 2010; Paoletti et al, 2013). NMDAR activation requires reliable and cell-specific release mechanisms depending on the physiological or pathological condition faced by the neuronal network.
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