2. Academic Validation
  3. Effects of sarcosine and N, N-dimethylglycine on NMDA receptor-mediated excitatory field potentials

Effects of sarcosine and N, N-dimethylglycine on NMDA receptor-mediated excitatory field potentials

  • J Biomed Sci. 2017 Feb 28;24(1):18. doi: 10.1186/s12929-016-0314-8.
Mei-Yi Lee 1,  Yi-Ruu Lin 1,  Yi-Shu Tu 2,  Yufeng Jane Tseng 2 3,  Ming-Huan Chan 4 5,  Hwei-Hsien Chen 6 7 8
Affiliations

Affiliations

  • 1 Master/PhD Program in Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, 97004, Taiwan.
  • 2 Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, 1, Sec. 4, Roosevelt Rd., Taipei, 10617, Taiwan.
  • 3 Department of Computer Science and Information Engineering, National Taiwan University, 1, Sec. 4, Roosevelt Rd., Taipei, 10617, Taiwan.
  • 4 Institute of Neuroscience, National Chengchi University, 64, Sec. 2, ZhiNan Road, Wenshan District, Taipei City, 11605, Taiwan. minghuan@nccu.edu.tw.
  • 5 Research Center for Mind, Brain, and Learning, National Chengchi University, 64, Sec. 2, ZhiNan Road, Wenshan District, Taipei City, 11605, Taiwan. minghuan@nccu.edu.tw.
  • 6 Master/PhD Program in Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, 97004, Taiwan. hwei@nhri.org.tw.
  • 7 Institute of Neuroscience, National Chengchi University, 64, Sec. 2, ZhiNan Road, Wenshan District, Taipei City, 11605, Taiwan. hwei@nhri.org.tw.
  • 8 Center for Neuropsychiatric Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County, 35053, Taiwan. hwei@nhri.org.tw.
PMID: 28245819 DOI: 10.1186/s12929-016-0314-8
Abstract

Background: Sarcosine, a glycine transporter type 1 inhibitor and an N-methyl-D-aspartate (NMDA) receptor co-agonist at the glycine binding site, potentiates NMDA Receptor function. Structurally similar to sarcosine, N,N-dimethylglycine (DMG) is also N-methyl glycine-derivative amino acid and commonly used as a dietary supplement. The present study compared the effects of sarcosine and DMG on NMDA receptor-mediated excitatory field potentials (EFPs) in mouse medial prefrontal cortex brain slices using a multi-electrode array system.

Results: Glycine, sarcosine and DMG alone did not alter the NMDA receptor-mediated EFPs, but in combination with glutamate, glycine and its N-methyl derivatives significantly increased the frequency and amplitude of EFPs. The enhancing effects of glycine analogs in combination with glutamate on EFPs were remarkably reduced by the glycine binding site antagonist 7-chlorokynurenate (7-CK). However, DMG, but not sarcosine, reduced the frequency and amplitude of EFPs elicited by co-application of glutamate plus glycine. D-cycloserine, a partial agonist at the glycine binding site on NMDA receptors, affected EFPs in a similar manner to DMG. Furthermore, DMG, but not sarcosine, reduced the frequencies and amplitudes of EFPs elicited by glutamate plus D-serine, another endogenous ligand for glycine binding site.

Conclusions: These findings suggest that sarcosine acts as a full agonist, yet DMG is a partial agonist at glycine binding site of NMDA receptors. The molecular docking analysis indicated that the interactions of glycine, sarcosine, and DMG to NMDA receptors are highly similar, supporting that the glycine binding site of NMDA receptors is a critical target site for sarcosine and DMG.

Keywords

7-chlorokynurenate; D-cycloserine; D-serine; Glycine binding site; N-methylglycine.

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