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Takagi S, Puhl MD, Anderson T, et al. Serine Racemase Expression by Striatal Neurons. Cell Mol Neurobiol. 2020;42(1):279-289doi: 10.1007/s10571-020-00880-9.
Takagi, S., Puhl, M. D., Anderson, T., Balu, D. T., & Coyle, J. T. (2022). Serine Racemase Expression by Striatal Neurons. Cellular and molecular neurobiology, 42(1), 279-289. https://doi.org/10.1007/s10571-020-00880-9
Takagi, Shunsuke, et al. "Serine Racemase Expression by Striatal Neurons." Cellular and molecular neurobiology vol. 42,1 (2022): 279-289. doi: https://doi.org/10.1007/s10571-020-00880-9
Takagi S, Puhl MD, Anderson T, Balu DT, Coyle JT. Serine Racemase Expression by Striatal Neurons. Cell Mol Neurobiol. 2022 Jan;42(1):279-289. doi: 10.1007/s10571-020-00880-9. Epub 2020 May 22. PMID: 32445040; PMCID: PMC7680280.
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Cell Mol Neurobiol. 2022 Jan;42(1):279-289. doi: 10.1007/s10571-020-00880-9. Epub 2020 May 22.

Serine Racemase Expression by Striatal Neurons.

Cellular and molecular neurobiology

Shunsuke Takagi, Matthew D Puhl, Thea Anderson, Darrick T Balu, Joseph T Coyle

Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
  2. Department of Psychiatry, Tokyo Medical and Dental University Hospital, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
  3. Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
  4. Laboratory for Psychiatric and Molecular Neuroscience, McLean Hospital, 115 Mill Street, Belmont, MA, 02478, USA.
  5. Department of Psychiatry, Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA.
  6. Translational Psychiatry Laboratory, McLean Hospital, 115 Mill Street, Belmont, MA, 02478, USA.
  7. Laboratory for Psychiatric and Molecular Neuroscience, McLean Hospital, 115 Mill Street, Belmont, MA, 02478, USA. [email protected].
  8. Department of Psychiatry, Harvard Medical School, 25 Shattuck Street, Boston, MA, 02115, USA. [email protected].

PMID: 32445040 PMCID: PMC7680280 DOI: 10.1007/s10571-020-00880-9

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.

© 2020. Springer Science+Business Media, LLC, part of Springer Nature.

Keywords: D-amino acid oxidase; D-serine; Gamma-aminobutyric acid; Glutamic acid decarboxylase; N-methyl-D-aspartic acid; Serine racemase

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