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Journal of Neural Transmission

, Volume 122, Issue 8, pp 1099–1103 | Cite as

Neuronal serine racemase regulates extracellular d-serine levels in the adult mouse hippocampus

  • Sayuri Ishiwata
  • Asami Umino
  • Darrick T. Balu
  • Joseph T. Coyle
  • Toru NishikawaEmail author
Translational Neurosciences - Short communication

Abstract

In the hippocampus of mice lacking the gene for serine racemase (SR), a d-serine synthesizing enzyme, in the CaMKIIα-expressing neurons, we observed a significant decrease in the extracellular concentration of d-serine, a coagonist for the N-methyl-d-aspartate type glutamate receptor (NMDAR), and NMDAR hypofunction as revealed by diminished extracellular taurine concentrations after an intra-hippocampal NMDA infusion when compared to the wild type controls. Therefore, the neuronal SR could regulate the extracellular d-serine signaling responsible for NMDAR activation in the hippocampus.

Keywords

CaMKIIα-expressing neurons Hippocampus In vivo microdialysis N-methyl-d-aspartate type glutamate receptor d-Serine Serine racemase 

Notes

Acknowledgments

This work was supported by the CREST (Core Research for Evolutional Science and Technology) program funded by the Ministry of Education, Culture, Sports, Science and Technology of Japan to TN research team including SI and AU. A postdoctoral National Research Service Award F32 MH090697 to DTB and grants R01MH05190 and P50MH0G0450 to JTC also supported this study. We thank the International Technology Exchange Society (an English editing agency: 3398 Tyler Drive Brunswick,OH 44212-3726 USA, Tel: 1-330-273-5409, Fax: 1-330-225-3834, E-mail: editing@adelphia.net) for their assistance in English editing for preparing our present manuscript, and are entirely responsible for the scientific content of this paper.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The present experiments were performed in accordance with the guidance of the Tokyo Medical and Dental University and were approved by the Animal Investigation Committee of the Institution.

References

  1. Balu DT, Coyle JT (2015) The NMDA receptor ‘glycine modulatory site’ in schizophrenia: d-serine, glycine, and beyond. Curr Opin Pharmacol 20C:109–115. doi: 10.1016/j.coph.2014.12.004 CrossRefGoogle Scholar
  2. Basu AC, Tsai GE, Ma CL, Ehmsen JT, Mustafa AK, Han L, Jiang ZI, Benneyworth MA, Froimowitz MP, Lange N, Snyder SH, Bergeron R, Coyle JT (2009) Targeted disruption of serine racemase affects glutamatergic neurotransmission and behavior. Mol Psychiatry 14:719–727. doi: 10.1038/mp.2008.130 PubMedCentralPubMedCrossRefGoogle Scholar
  3. Benneyworth MA, Li Y, Basu AC, Bolshakov VY, Coyle JT (2012) Cell selective conditional null mutations of serine racemase demonstrate a predominate localization in cortical glutamatergic neurons. Cell Mol Neurobiol 32:613–624. doi: 10.1007/s10571-012-9808-4 PubMedCrossRefGoogle Scholar
  4. Ishiwata S, Ogata S, Umino A, Shiraku H, Ohashi Y, Kajii Y, Nishikawa T (2013a) Increasing effects of S-methyl-l-cysteine on the extracellular d-serine concentrations in the rat medial frontal cortex. Amino Acids 44:1391–1395. doi: 10.1007/s00726-013-1464-6 PubMedCrossRefGoogle Scholar
  5. Ishiwata S, Umino A, Umino M, Yorita K, Fukui K, Nishikawa T (2013b) Modulation of extracellular d-serine content by calcium permeable AMPA receptors in rat medial prefrontal cortex as revealed by in vivo microdialysis. Int J Neuropsychopharmacol 16:1395–1406. doi: 10.1017/S1461145712001484 PubMedCrossRefGoogle Scholar
  6. Lehmann A, Lazarewicz JW, Zeise M (1985) N-Methylaspartate-evoked liberation of taurine and phosphoethanolamine in vivo: site of release. J Neurochem 45:1172–1177PubMedCrossRefGoogle Scholar
  7. Maucler C, Pernot P, Vasylieva N, Pollegioni L, Marinesco S (2013) In vivo d-serine hetero-exchange through alanine-serine-cysteine (ASC) transporters detected by microelectrode biosensors. ACS Chem Neurosci 4(5):772–781. doi: 10.1021/cn4000549 PubMedCentralPubMedCrossRefGoogle Scholar
  8. Menendez N, Herreras O, Solis JM, Herranz AS, Martin del Rio R (1989) Extracellular taurine increase in rat hippocampus evoked by specific glutamate receptor activation is related to the excitatory potency of glutamate agonists. Neurosci Lett 102:64–69PubMedCrossRefGoogle Scholar
  9. Nishikawa T (2011) Analysis of free d-serine in mammals and its biological relevance. J Chromatogr B Analyt Technol Biomed Life Sci 879:3169–3183. doi: 10.1016/j.jchromb.2011.08.030 PubMedCrossRefGoogle Scholar
  10. Paxinos G, Franklin K (2004) The mouse brain in stereotaxic coordinates, 2nd edn. Elsevier Academic Press, AmsterdamGoogle Scholar
  11. Rodriguez-Navarro JA, Gonzalo-Gobernado R, Herranz AS, Gonzlez-Vigueras JM, Solis JM (2009) High potassium induces taurine release by osmosensitive and osmoresistant mechanisms in the rat hippocampus in vivo. J Neurosci Res 87:208–217. doi: 10.1002/jnr.21818 PubMedCrossRefGoogle Scholar
  12. Rosenberg D, Artoul S, Segal AC, Kolodney G, Radzishevsky I, Dikopoltsev E, Foltyn VN, Inoue R, Mori H, Billard JM, Wolosker H (2013) Neuronal d-serine and glycine release via the Asc-1 transporter regulates NMDA receptor-dependent synaptic activity. J Neurosci 33(8):3533–3544. doi: 10.1523/JNEUROSCI.3836-12.2013 PubMedCrossRefGoogle Scholar
  13. Schweizer C, Balsiger S, Bluethmann H, Mansuy IM, Fritschy JM, Mohler H, Luscher B (2003) The gamma 2 subunit of GABA(A) receptors is required for maintenance of receptors at mature synapses. Mol Cell Neurosci 24:442–450PubMedCrossRefGoogle Scholar
  14. Shibanoki S, Kogure M, Sugahara M, Ishikawa K (1993) Effect of systemic administration of N-methyl-d-aspartic acid on extracellular taurine level measured by microdialysis in the hippocampal CA1 field and striatum of rats. J Neurochem 61:1698–1704PubMedCrossRefGoogle Scholar
  15. Wolosker H (2007) NMDA receptor regulation by d-serine: new findings and perspectives. Mol Neurobiol 36(2):152–164PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  • Sayuri Ishiwata
    • 1
  • Asami Umino
    • 1
  • Darrick T. Balu
    • 2
    • 3
  • Joseph T. Coyle
    • 2
    • 3
  • Toru Nishikawa
    • 1
    Email author
  1. 1.Department of Psychiatry and Behavioral Sciences, Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityBunkyo-kuJapan
  2. 2.Department of PsychiatryHarvard Medical SchoolBostonUSA
  3. 3.Laboratory for Psychiatric and Molecular NeuroscienceMcLean HospitalBelmontUSA

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