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

Yamanaka, Masahiro; Miyoshi, Y.; Ohide, Hiroko; Hamase, Kenji; Konno, Ryuichi

doi:10.1007/s00726-012-1384-x

Cited by 50 publications

(38 citation statements)

References 112 publications

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“…A role for DAO in the VTA cannot be assumed just by virtue of its expression therein, since DAO mRNA and immunoreactivity are also detected in frontal cortex (Moreno et al, 1999; Hashimoto et al, 2007; Verrall et al, 2007), yet there is limited evidence for functionality of cortical DAO, and cortical D-serine concentrations are not elevated in the ddY/DAO − mouse (Yamanaka et al, 2012). Our in vivo microdialysis data suggest that VTA DAO is indeed functional (complementing the observations of Fernandez-Espejo et al, 2008), since local injection of the DAO inhibitor sodium benzoate increased extracellular dopamine and its metabolites in medial frontal cortex (Figures 3A–C).…”

Section: Discussionmentioning

confidence: 99%

“…Perhaps DAO inhibition affects a substrate other than D-serine, for example D-alanine, which is a high affinity NMDA receptor co-agonist (Tanii et al, 1994) metabolized by DAO (Molla et al, 2006; Horio et al, 2009), and whose levels rise markedly in rodents lacking DAO (Yamanaka et al, 2012). Alternatively, the injected D-serine may be rapidly removed from the synapse via a transporter (Helboe et al, 2003; Rutter et al, 2007; Burnet et al, 2008b; Sikka et al, 2010), or metabolized by serine racemase (Foltyn et al, 2005; Strisovsky et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

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D-amino acid oxidase is expressed in the ventral tegmental area and modulates cortical dopamine

Betts

Schweimer

Burnham

et al. 2014

Front. Synaptic Neurosci.

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D-amino acid oxidase (DAO, DAAO) degrades the NMDA receptor co-agonist D-serine, modulating D-serine levels and thence NMDA receptor function. DAO inhibitors are under development as a therapy for schizophrenia, a disorder involving both NMDA receptor and dopaminergic dysfunction. However, a direct role for DAO in dopamine regulation has not been demonstrated. Here, we address this question in two ways. First, using in situ hybridization and immunohistochemistry, we show that DAO mRNA and immunoreactivity are present in the ventral tegmental area (VTA) of the rat, in tyrosine hydroxylase (TH)-positive and -negative neurons, and in glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes. Second, we show that injection into the VTA of sodium benzoate, a DAO inhibitor, increases frontal cortex extracellular dopamine, as measured by in vivo microdialysis and high performance liquid chromatography. Combining sodium benzoate and D-serine did not enhance this effect, and injection of D-serine alone affected dopamine metabolites but not dopamine. These data show that DAO is expressed in the VTA, and suggest that it impacts on the mesocortical dopamine system. The mechanism by which the observed effects occur, and the implications of these findings for schizophrenia therapy, require further study.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

D-amino acid oxidase is expressed in the ventral tegmental area and modulates cortical dopamine

Betts

Schweimer

Burnham

et al. 2014

Front. Synaptic Neurosci.

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“…Therefore, SR might regulate the physiological level of D-serine by racemization activity to synthesize D-serine and by α , β -elimination activity to degrade D-serine. DAO is the flavoprotein that converts D-serine to produce the corresponding alpha keto acid, hydrogen peroxide, and ammonia [11]. …”

Section: D-serinementioning

confidence: 99%

“…D-Amino acids are enantiomers of L-amino acids and have been considered to be absent and unnatural amino acids in mammals for a long time. However, the recent development of sensitive analytical methods elucidated the presence of D-amino acids, such as D-serine, D-aspartate, and D-alanine, in mammals [9–11]. Moreover, studies on the enzymes that synthesize or metabolize D-amino acids have also clarified the localization and functions of D-amino acids in the nervous and endocrine systems and found that D-amino acid synthesis and metabolism are physiologically regulated [12–15].…”

Section: Introductionmentioning

confidence: 99%

D-Amino Acids in the Nervous and Endocrine Systems

Kiriyama

Nochi

2016

Scientifica

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Amino acids are important components for peptides and proteins and act as signal transmitters. Only L-amino acids have been considered necessary in mammals, including humans. However, diverse D-amino acids, such as D-serine, D-aspartate, D-alanine, and D-cysteine, are found in mammals. Physiological roles of these D-amino acids not only in the nervous system but also in the endocrine system are being gradually revealed. N-Methyl-D-aspartate (NMDA) receptors are associated with learning and memory. D-Serine, D-aspartate, and D-alanine can all bind to NMDA receptors. H2S generated from D-cysteine reduces disulfide bonds in receptors and potentiates their activity. Aberrant receptor activity is related to diseases of the central nervous system (CNS), such as Alzheimer's disease, amyotrophic lateral sclerosis, and schizophrenia. Furthermore, D-amino acids are detected in parts of the endocrine system, such as the pineal gland, hypothalamus, pituitary gland, pancreas, adrenal gland, and testis. D-Aspartate is being investigated for the regulation of hormone release from various endocrine organs. Here we focused on recent findings regarding the synthesis and physiological functions of D-amino acids in the nervous and endocrine systems.

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“…However, in the current ecological system on Earth, L-amino acids are predominantly observed in the organisms. On the other hand, the presence of D-amino acids is normally in very trace amounts [5,6], and the origin of this "homochirality" is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Enantioselective Determination of Extraterrestrial Amino Acids Using a Two-Dimensional Chiral High-Performance Liquid Chromatographic System

et al. 2014

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A two-dimensional chiral high-performance liquid chromatographic (2D-HPLC) system has been established for the analysis of extraterrestrial amino acids. As the targets, 8 chiral amino acids (alanine (Ala), valine (Val), 2-aminobutyric acid (2AB), norvaline (nVal), N-methylalanine (N-MeAla), isovaline (iVal), 3AB and 3-aminoisobutyric acid (3AIB)) and 5 non-chiral amino acids (glycine (Gly), β-Ala, γ-aminobutyric acid (GABA), sarcosine (Sar) and 2AIB) were selected. These amino acids were tagged with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), and non-enantioselectively separated by a capillary monolithic ODS column in the first dimension. The target fractions were automatically introduced into the second dimension and further separated by Pirkle-type enantioselective columns. By using this system, the 2D-HPLC separation of 21 components in small particles of a carbonaceous chondrite (Yamato 791191, Antarctic CM2 meteorite) could be successfully performed, and all of the target amino acids were observed. The D/L ratios of the chiral molecules are almost 50/50 for all of the tested proteinogenic and non-proteinogenic amino acids.

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

Cited by 50 publications

References 112 publications

D-amino acid oxidase is expressed in the ventral tegmental area and modulates cortical dopamine

D-amino acid oxidase is expressed in the ventral tegmental area and modulates cortical dopamine

D-Amino Acids in the Nervous and Endocrine Systems

Enantioselective Determination of Extraterrestrial Amino Acids Using a Two-Dimensional Chiral High-Performance Liquid Chromatographic System

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