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

Masahiro Yamanaka, Yurika Miyoshi, Hiroko Ohide, Kenji Hamase, Ryuichi Konno

Research output: Contribution to journalReview article

28 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1811-1821
Number of pages11
JournalAmino Acids
Volume43
Issue number5
DOIs
Publication statusPublished - Nov 1 2012

Fingerprint

D-Amino-Acid Oxidase
Rodentia
Brain
Serine
Amino Acids
N-Methyl-D-Aspartate Receptors
Synaptic Transmission
Basic Amino Acids
Rhombencephalon
Stereoisomerism
Neuronal Plasticity
Amyotrophic Lateral Sclerosis
Prosencephalon
Neurology
Schizophrenia
Central Nervous System
Plasticity
Rats
Pain

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

D-Amino acids in the brain and mutant rodents lacking D-amino-acid oxidase activity. / Yamanaka, Masahiro; Miyoshi, Yurika; Ohide, Hiroko; Hamase, Kenji; Konno, Ryuichi.

In: Amino Acids, Vol. 43, No. 5, 01.11.2012, p. 1811-1821.

Research output: Contribution to journalReview article

Yamanaka, Masahiro ; Miyoshi, Yurika ; Ohide, Hiroko ; Hamase, Kenji ; Konno, Ryuichi. / D-Amino acids in the brain and mutant rodents lacking D-amino-acid oxidase activity. In: Amino Acids. 2012 ; Vol. 43, No. 5. pp. 1811-1821.
@article{5731e25669974ba7b14c2c1e281d97dc,
title = "D-Amino acids in the brain and mutant rodents lacking D-amino-acid oxidase activity",
abstract = "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.",
author = "Masahiro Yamanaka and Yurika Miyoshi and Hiroko Ohide and Kenji Hamase and Ryuichi Konno",
year = "2012",
month = "11",
day = "1",
doi = "10.1007/s00726-012-1384-x",
language = "English",
volume = "43",
pages = "1811--1821",
journal = "Amino Acids",
issn = "0939-4451",
publisher = "Springer Wien",
number = "5",

}

TY - JOUR

T1 - D-Amino acids in the brain and mutant rodents lacking D-amino-acid oxidase activity

AU - Yamanaka, Masahiro

AU - Miyoshi, Yurika

AU - Ohide, Hiroko

AU - Hamase, Kenji

AU - Konno, Ryuichi

PY - 2012/11/1

Y1 - 2012/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84868092353&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84868092353&partnerID=8YFLogxK

U2 - 10.1007/s00726-012-1384-x

DO - 10.1007/s00726-012-1384-x

M3 - Review article

C2 - 22892863

AN - SCOPUS:84868092353

VL - 43

SP - 1811

EP - 1821

JO - Amino Acids

JF - Amino Acids

SN - 0939-4451

IS - 5

ER -