title: The serine shuttle between glia and neurons: implications for neurotransmission and neurodegeneration.
abstract: D-Serine is a physiological co-agonist of NMDARs (N-methyl-D-aspartate receptors) required for neurotransmission, synaptic plasticity and neurotoxicity. There is no consensus, however, on the relative roles of neurons and astrocytes in D-serine signalling. The effects of D-serine had been attributed to its role as a gliotransmitter specifically produced and released by astrocytes. In contrast, recent studies indicate that neurons regulate their own NMDARs by releasing D-serine via plasma membrane transporters and depolarization-sensitive pathways. Only a minority of astrocytes contain authentic D-serine, whereas neuronal D-serine accounts for up to 90% of the total D-serine pool. Neuronal and glial D-serine production requires astrocytic L-serine generated by a 3-phosphoglycerate dehydrogenase-dependent pathway. These findings support a model whereby astrocyte-derived L-serine shuttles to neurons to fuel the synthesis of D-serine by serine racemase. We incorporate these new findings in a revised model of serine dynamics, called the glia-neuron serine shuttle, which highlights the role of glia-neuron cross-talk for optimal NMDAR activity and brain development.
authors.affiliation: *Department of Biochemistry, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 31096, Israel.
authors.forename: Herman
authors.initials: H
authors.lastname: Wolosker
authors.forename: Inna
authors.initials: I
authors.lastname: Radzishevsky
mesh_terms: D006801:Humans; D009410:Nerve Degeneration / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D009435:Synaptic Transmission
chemical_list: D012694:Serine