التفاصيل البيبلوغرافية
| العنوان: |
Neuronal D-Serine and Glycine Release Via the Asc-1 Transporter Regulates NMDA Receptor-Dependent Synaptic Activity. |
| المؤلفون: |
Rosenberg, Dina, Artoul, Samar, Segal, Adi C., Kolodney, Goren, Radzishevsky, Inna, Dikopoltsev, Elena, Foltyn, Veronika N., Inoue, Ran, Mori, Hisashi, Billard, Jean-Marie, Wolosker, Herman |
| المصدر: |
Journal of Neuroscience; 2/20/2013, Vol. 33 Issue 8, p3533-3544, 12p |
| مصطلحات موضوعية: |
NEURAL circuitry, SERINE, GLYCINE, LONG-term potentiation, AMINO acid transport, CARRIER proteins, METHYL aspartate receptors, NEURAL transmission |
| مستخلص: |
D-Serine and glycine are coagonists of NMDA receptors (NMDARs), but their relative contributions for several NMDAR-dependent processes are unclear. We now report that the alanine-serine-cysteine transporter-1 (Asc-1) mediates release of both D-serine and glycine from neurons, and, in turn, this modulates NMDAR synaptic activity. Asc-1 antiporter activity is enhanced by D-isoleucine (D-Ile), which releases D-serine and glycine from Asc-1 -transfected cells, primary neuronal cultures, and hippocampal slices. D-Ile has no effect on astrocytes, which do not express Asc-1. We show that D-Ile enhances the long-term potentiation (LTP) in rat and mouse hippocampal CA1 by stimulating Asc-1 -mediated endogenous D-serine release. D-Ile effects on synaptic plasticity are abolished by enzymatically depleting D-serine or by using serine racemase knock-out (SR-KO) mice, confirming its specificity and supporting the notion that LTP depends mostly on D-serine release. Conversely, our data also disclose a role of glycine in activating synaptic NMDARs. Although acute enzymatic depletion of D-serine also drastically decreases the isolated NMDAR synaptic potentials, these responses are still enhanced by D-Ile. Furthermore, NMDAR synaptic potentials are preserved in SR-KO mice and are also enhanced by D-Ile, indicating that glycine overlaps with D-serine binding at synaptic NMDARs. Altogether, our results disclose a novel role of Asc-1 in regulating NMDAR-dependent synaptic activity by mediating concurrent non-vesicular release of D-serine and glycine. Our data also highlight an important role of neuron-derived D-serine and glycine, indicating that astrocytic D-serine is not solely responsible for activating synaptic NMDARs. [ABSTRACT FROM AUTHOR] |
|
Copyright of Journal of Neuroscience is the property of Society for Neuroscience and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder