ArticleCellular and molecular neurobiology2022
Serine Racemase Expression by Striatal Neurons.
Article in Cellular and molecular neurobiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.
- Rational and Translational Implications of D-Amino Acids for Treatment-Resistant Schizophrenia: From Neurobiology to the Clinics.Biomolecules · 2022Pooled it
- Post-translational regulation of human D-3-phosphoglycerate dehydrogenase in Alzheimer's disease.Protein science : a publication of the Protein Society · 2026Article
- Article
- Information-Rich, Dual-FunctionJournal of the American Chemical Society · 2023Article
- Dopaminergic neuromodulation of prefrontal cortex activity requires the NMDA receptor coagonist d-serine.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Factors regulating serine racemase and d-amino acid oxidase expression in the mouse striatum.Brain research · 2021Article
- Postsynaptic Serine Racemase Regulates NMDA Receptor Function.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
D-serine is synthesized by serine racemase (SR) and is a co-agonist at forebrain N-methyl-D-aspartate receptors (NMDARs). D-serine and SR are expressed primarily in neurons, but not in quiescent astrocytes. In this study, we examined the localization of D-serine and SR in the mouse striatum and the effects of genetically silencing SR expression in GABAergic interneurons (iSR-/-). iSR-/- mice had substantially reduced SR expression almost exclusively in striatum, but only exhibited marginal D-serine reduction. SR positive cells in the striatum showed strong co-localization with dopamine- and cyclic AMP-regulated neuronal phosphoprotein (DARPP32) in wild type mice. Transgenic fluorescent reporter mice for either the D1 or D2 dopamine receptors exhibited a 65:35 ratio for co-localization with D1and D2 receptor positive cells, respectively. These results indicate that GABAergic medium spiny neurons receiving dopaminergic inputs in striatum robustly and uniformly express SR. In behavioral tests, iSR-/- mice showed a blunted response to the hedonic and stimulant effects of cocaine, without affecting anxiety-related behaviors. Because the cocaine effects have been shown in the constitutive SR-/- mice, the restriction of the blunted response to cocaine to iSR-/- mice reinforces the conclusion that D-serine in striatal GABAergic neurons plays an important role in mediating dopaminergic stimulant effects. Results in this study suggest that SR in striatal GABAergic neurons is synthesizing D-serine, not as a glutamatergic co-transmitter, but rather as an autocrine whereby the GABAergic neurons control the excitability of their NMDARs by determining the availability of the co-agonist, D-serine.
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Registered trials
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