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Trends Neurosci. 2016 Nov;39(11):712-721. doi: 10.1016/j.tins.2016.09.007. Epub 2016 Oct 11.

The Rise and Fall of the d-Serine-Mediated Gliotransmission Hypothesis.

Author information

1
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.
2
Department of Psychiatry, Harvard Medical School, Boston, MA, USA; Translational Psychiatry Laboratory, McLean Hospital, Belmont, MA 02478, USA. Electronic address: dbalu@mclean.harvard.edu.
3
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.

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.

KEYWORDS:

N-methyl d-aspartate receptor; d-serine; gliotransmission; glycine; serine racemase; synaptic plasticity

PMID:
27742076
PMCID:
PMC5113294
DOI:
10.1016/j.tins.2016.09.007
[Indexed for MEDLINE]
Free PMC Article

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