title: The Rise and Fall of the d-Serine-Mediated Gliotransmission Hypothesis.
abstract: d-Serine modulates N-methyl d-aspartate receptors (NMDARs) and regulates synaptic plasticity, neurodevelopment, and learning and memory. However, the primary site of d-serine synthesis and release remains controversial, with some arguing that it is a gliotransmitter and others defining it as a neuronal cotransmitter. Results from several laboratories using different strategies now show that the biosynthetic enzyme of d-serine, serine racemase (SR), is expressed almost entirely by neurons, with few astrocytes appearing to contain d-serine. Cell-selective suppression of SR expression demonstrates that neuronal, rather than astrocytic d-serine, modulates synaptic plasticity. Here, we propose an alternative conceptualization whereby astrocytes affect d-serine levels by synthesizing l-serine that shuttles to neurons to fuel the neuronal synthesis of d-serine.
authors.affiliation: Department of Biochemistry, Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 31096, Israel. Electronic address: hwolosker@tx.technion.ac.il.
authors.forename: Herman
authors.initials: H
authors.lastname: Wolosker
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Translational Psychiatry Laboratory, McLean Hospital, Belmont, MA 02478, USA. Electronic address: dbalu@mclean.harvard.edu.
authors.forename: Darrick T
authors.initials: DT
authors.lastname: Balu
authors.affiliation: Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Laboratory of Psychiatric and Molecular Neuroscience, McLean Hospital, Belmont, MA 02478, USA. Electronic address: joseph_coyle@hms.harvard.edu.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Coyle
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D006801:Humans; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine
keywords: N-methyl d-aspartate receptor; d-serine; gliotransmission; glycine; serine racemase; synaptic plasticity