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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

View Article: PubMed Central - PubMed

ABSTRACT

In the brain, D-amino acid oxidase (DAO/DAAO) mainly oxidizes D-serine, a co-agonist of the N-methyl-D-aspartate (NMDA) receptors. Thus, DAO can regulate the function of NMDA receptors via D-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 DAO 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 DAOA 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 DAO and DAOA CpG sites in the cerebellum and frontal cortex of control human post-mortem brain obtained from Gene Expression Omnibus datasets. Indeed, DAO and DAOA CpG sites in the cerebellum were significantly more methylated than those in the frontal cortex. While investigating lifespan effects, we found that DAO mRNA levels were positively correlated with age <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.

No MeSH data available.


DAO mRNA levels across five different age groups in six regions of human post-mortem brain (A–F). Data presented as scatter plots. Kruskal–Wallis test followed by pairwise comparisons with the Mann–Whitney test (∗p < 0.005) was performed to assess the differences in DAO mRNA levels between different age groups across six brain regions.
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Figure 2: DAO mRNA levels across five different age groups in six regions of human post-mortem brain (A–F). Data presented as scatter plots. Kruskal–Wallis test followed by pairwise comparisons with the Mann–Whitney test (∗p < 0.005) was performed to assess the differences in DAO mRNA levels between different age groups across six brain regions.

Mentions: We found statistically significant (p < 0.05) differences in DAO mRNA levels across the five different age groups, as assessed by the Kruskal–Wallis test, in the cerebellum, brainstem (Figure 2B), amygdala, striatum, and thalamus. However, differences in DAO mRNA levels were found to be statistically non-significant in the frontal cortex (Figure 2F). Pair-wise comparisons using the Mann–Whitney test showed statistically significant differences (p < 0.005) in DAO mRNA levels between age groups 0–2 years and >61 years in the cerebellum (Figure 2A) and striatum (Figure 2D), between prenatal and >61 years in the amygdala (Figure 2C), and between prenatal and >61 years, 0–2 years and 36–60 years, 0–2 years and >61 years in the thalamus (Figure 2E).


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
DAO mRNA levels across five different age groups in six regions of human post-mortem brain (A–F). Data presented as scatter plots. Kruskal–Wallis test followed by pairwise comparisons with the Mann–Whitney test (∗p < 0.005) was performed to assess the differences in DAO mRNA levels between different age groups across six brain regions.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382383&req=5

Figure 2: DAO mRNA levels across five different age groups in six regions of human post-mortem brain (A–F). Data presented as scatter plots. Kruskal–Wallis test followed by pairwise comparisons with the Mann–Whitney test (∗p < 0.005) was performed to assess the differences in DAO mRNA levels between different age groups across six brain regions.
Mentions: We found statistically significant (p < 0.05) differences in DAO mRNA levels across the five different age groups, as assessed by the Kruskal–Wallis test, in the cerebellum, brainstem (Figure 2B), amygdala, striatum, and thalamus. However, differences in DAO mRNA levels were found to be statistically non-significant in the frontal cortex (Figure 2F). Pair-wise comparisons using the Mann–Whitney test showed statistically significant differences (p < 0.005) in DAO mRNA levels between age groups 0–2 years and >61 years in the cerebellum (Figure 2A) and striatum (Figure 2D), between prenatal and >61 years in the amygdala (Figure 2C), and between prenatal and >61 years, 0–2 years and 36–60 years, 0–2 years and >61 years in the thalamus (Figure 2E).

View Article: PubMed Central - PubMed

ABSTRACT

In the brain, D-amino acid oxidase (DAO/DAAO) mainly oxidizes D-serine, a co-agonist of the N-methyl-D-aspartate (NMDA) receptors. Thus, DAO can regulate the function of NMDA receptors via D-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 DAO 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 DAOA 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 DAO and DAOA CpG sites in the cerebellum and frontal cortex of control human post-mortem brain obtained from Gene Expression Omnibus datasets. Indeed, DAO and DAOA CpG sites in the cerebellum were significantly more methylated than those in the frontal cortex. While investigating lifespan effects, we found that DAO 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.

No MeSH data available.