AUTHOR=Jagannath Vinita , Marinova Zoya , Monoranu Camelia-Maria , Walitza Susanne , Grünblatt Edna 

TITLE=Expression of D-Amino Acid Oxidase (DAO/DAAO) and D-Amino Acid Oxidase Activator (DAOA/G72) during Development and Aging in the Human Post-mortem Brain

JOURNAL=Frontiers in Neuroanatomy

VOLUME=11

YEAR=2017

URL=https://www.frontiersin.org/journals/neuroanatomy/articles/10.3389/fnana.2017.00031

DOI=10.3389/fnana.2017.00031

ISSN=1662-5129

ABSTRACT=<p>In the brain, <sc>D</sc>-amino acid oxidase (DAO/DAAO) mainly oxidizes <sc>D</sc>-serine, a co-agonist of the <italic>N</italic>-methyl-<sc>D</sc>-aspartate (NMDA) receptors. Thus, DAO can regulate the function of NMDA receptors via <sc>D</sc>-serine breakdown. Furthermore, DAO activator (DAOA)/G72 has been reported as both DAOA and repressor. The co-expression of DAO and DAOA genes and proteins in the human brain is not yet elucidated. The aim of this study was to understand the regional and age span distribution of DAO and DAOA (mRNA and protein) in a concomitant manner. We determined DAO and DAOA mRNA and protein expression across six brain regions in normal human post-mortem brain samples (16 weeks of gestation to 91 years) using quantitative real-time reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. We found higher expression of <italic>DAO</italic> mRNA in the cerebellum, whereas lower expression of DAO protein in the cerebellum compared to the other brain regions studied, which suggests post-transcriptional regulation. We detected DAOA protein but not <italic>DAOA</italic> mRNA in all brain regions studied, suggesting a tightly regulated expression. To understand this regulation at the transcriptional level, we analyzed DNA methylation levels at <italic>DAO</italic> and <italic>DAOA</italic> CpG sites in the cerebellum and frontal cortex of control human post-mortem brain obtained from Gene Expression Omnibus datasets. Indeed, <italic>DAO</italic> and <italic>DAOA</italic> CpG sites in the cerebellum were significantly more methylated than those in the frontal cortex. While investigating lifespan effects, we found that <italic>DAO</italic> mRNA levels were positively correlated with age &lt;2 years in the cerebellum and amygdala. We also detected a significant positive correlation (controlled for age) between DAO and DAOA protein in all of the brain regions studied except for the frontal cortex. In summary, DAO and DAOA expression in the human brain are both age and brain region dependent.</p>