D-Amino acid oxidase activity and expression are increased in schizophrenia

Burnet, Philip W.J.; Eastwood, Sharon L.; Bristow, Greg C.; Godlewska, Beata R.; Sikka, Pilleriin; Walker, Mary A.; Harrison, Paul J.

doi:10.1038/mp.2008.47

Cited by 92 publications

(72 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is interesting to note that two recent independent studies revealed that DAAO expression and activity are elevated in schizophrenia (Burnet et al, 2008;Madeira et al, 2008). Because the highest DAAO activity is found in the kidneys (Curti et al, 1992), a substantial amount of orally administered D-serine is metabolized there.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of Oral d-Serine in d-Amino Acid Oxidase Knockout Mice

et al. 2012

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of Oral d-Serine in d-Amino Acid Oxidase Knockout Mice

et al. 2012

View full text Add to dashboard Cite

“…19 A third study, in a separate and larger cohort, confirmed elevated cerebellar DAO mRNA and activity in schizophrenia. 11 Increased DAO activity was also found in the parietal cortex, 12 while Bendikov et al 18 found unchanged DAO protein in the prefrontal cortex and hippocampus. Taken together, these data …”

Section: Dao Expression and Activity In Schizophreniamentioning

confidence: 99%

“…Increased cerebellar DAO activity in schizophrenia may be caused by one of several reasons. The fact that DAO mRNA is increased (and correlates with DAO activity) 11 indicates that the mechanism is likely to involve transcriptional regulation. However, as noted, it does not seem to be related to the DAO genotype; 11 in any event, as DAO risk alleles are carried by only a minority of cases and by some control subjects, this could not explain the observed differences between diagnostic groups.…”

Section: /13mentioning

confidence: 99%

“…The fact that DAO mRNA is increased (and correlates with DAO activity) 11 indicates that the mechanism is likely to involve transcriptional regulation. However, as noted, it does not seem to be related to the DAO genotype; 11 in any event, as DAO risk alleles are carried by only a minority of cases and by some control subjects, this could not explain the observed differences between diagnostic groups. G72 mRNA is reportedly increased in schizophrenia, 182 and if it is a DAO activator, then this might be a contributory factor; however, the uncertainties noted above regarding the relationship between G72 and DAO, and regarding the expression of G72 in the brain, make this speculative.…”

Section: /13mentioning

confidence: 99%

“…Flavin adenine dinucleotide binding is notably weaker in Increased DAO activity in schizophrenia 11,12 Abbreviations: DAO, D-amino acid oxidase; LTP, long-term potentiation; PCP, phencyclidine. * * * * * Figure 1 The D-amino acid oxidase (DAO) gene and transcript.…”

mentioning

confidence: 99%

See 2 more Smart Citations

The neurobiology of D-amino acid oxidase and its involvement in schizophrenia

et al. 2009

Self Cite

View full text Add to dashboard Cite

D-amino acid oxidase (DAO) is a flavoenzyme that metabolizes certain D-amino acids, notably the endogenous N-methyl D-aspartate receptor (NMDAR) co-agonist, D-serine. As such, it has the potential to modulate the function of NMDAR and to contribute to the widely hypothesized involvement of NMDAR signalling in schizophrenia. Three lines of evidence now provide support for this possibility: DAO shows genetic associations with the disorder in several, although not all, studies; the expression and activity of DAO are increased in schizophrenia; and DAO inactivation in rodents produces behavioural and biochemical effects, suggestive of potential therapeutic benefits. However, several key issues remain unclear. These include the regional, cellular and subcellular localization of DAO, the physiological importance of DAO and its substrates other than D-serine, as well as the causes and consequences of elevated DAO in schizophrenia. Herein, we critically review the neurobiology of DAO, its involvement in schizophrenia, and the therapeutic value of DAO inhibition. This review also highlights issues that have a broader relevance beyond DAO itself: how should we weigh up convergent and cumulatively impressive, but individually inconclusive, pieces of evidence regarding the role that a given gene may have in the aetiology, pathophysiology and pharmacotherapy of schizophrenia? Molecular Psychiatry (2010) 15, 122-137;

show abstract

Astrocytic d‐amino acid oxidase degrades d‐serine in the hindbrain

Gonda¹,

Ishii

Mita

et al. 2022

FEBS Letters

View full text Add to dashboard Cite

Edited by Ned ManteiD-Serine modulates excitatory neurotransmission by binding to N-methyl-D-aspartate glutamate receptors. D-Amino acid oxidase (DAO) degrades D-amino acids, such as D-serine, in the central nervous system, and is associated with neurological and psychiatric disorders. However, cell types that express brain DAO remain controversial, and whether brain DAO influences systemic D-amino acids in addition to brain D-serine remains unclear. Here, we created astrocyte-specific DAO-conditional knockout mice. Knockout in glial fibrillary acidic protein-positive cells eliminated DAO expression in the hindbrain and increased D-serine levels significantly in the cerebellum. Brain DAO did not influence levels of D-amino acids in the forebrain or periphery. These results show that astrocytic DAO regulates D-serine specifically in the hindbrain.

show abstract

D-Amino acid oxidase activity and expression are increased in schizophrenia

Cited by 92 publications

References 10 publications

Pharmacokinetics of Oral d-Serine in d-Amino Acid Oxidase Knockout Mice

Pharmacokinetics of Oral d-Serine in d-Amino Acid Oxidase Knockout Mice

The neurobiology of D-amino acid oxidase and its involvement in schizophrenia

Astrocytic d‐amino acid oxidase degrades d‐serine in the hindbrain

Contact Info

Product

Resources

About