Amino Acids

, Volume 43, Issue 5, pp 1811–1821 | Cite as

d-Amino acids in the brain and mutant rodents lacking d-amino-acid oxidase activity

  • Masahiro Yamanaka
  • Yurika Miyoshi
  • Hiroko Ohide
  • Kenji Hamase
  • Ryuichi KonnoEmail author
Review Article


d-Amino acids are stereoisomers of l-amino acids. They are often called unnatural amino acids, but several d-amino acids have been found in mammalian brains. Among them, d-serine is abundant in the forebrain and functions as a co-agonist of NMDA receptors to enhance neurotransmission. d-Amino-acid oxidase (DAO), which degrades neutral and basic d-amino acids, is mainly present in the hindbrain. DAO catabolizes d-serine and, therefore, modulates neurotransmission. In the brains of mutant mice and rats lacking DAO activity, the amounts of d-serine and other d-amino acids are markedly increased. Mutant mice manifested behavioral changes characteristic of altered NMDA receptor activity, likely due to increased levels of d-serine. d-Serine and DAO have been demonstrated to play important roles in cerebellar development and synaptic plasticity. They have also implicated in amyotrophic lateral sclerosis and pain response. There have also been several lines of evidence correlating DAO with schizophrenia. Taken together, the experiments indicate that d-amino acids and DAO have pivotal functions in the central nervous system.


d-Amino-acid oxidase d-Serine Mouse Rat NMDA receptor Neuropsychological diseases 



Adrenocorticotropic hormone


Amyotrophic lateral sclerosis




Central nervous system


d-Amino-acid oxidase


Excitatory postsynaptic current


Long-term depression


Long-term potentiation










Serine racemase


Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Masahiro Yamanaka
    • 1
  • Yurika Miyoshi
    • 2
  • Hiroko Ohide
    • 1
  • Kenji Hamase
    • 2
  • Ryuichi Konno
    • 1
    Email author
  1. 1.Department of Pharmaceutical SciencesInternational University of Health and WelfareOhtawaraJapan
  2. 2.Graduate School of Pharmaceutical SciencesKyushu UniversityFukuokaJapan

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