2006 Fiscal Year Final Research Report Summary
DNA methylation status of monoamine-related genes in post-mortem brains of schizophrenia
| Project/Area Number |
17591225
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
IKEMOTO Keiko Fukushima Medical University, Faculty of Medicine, Dept. of Psychiatry, Associate Prof., 医学部, 准教授 (90184449)
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| Co-Investigator(Kenkyū-buntansha) |
HOMMA Yoshimi Fukushima Medical University, Faculty of Medicine, Dept. of Psychiatry, Professor, 医学部, 教授 (60192324)
NIWA Shin-ichi Fukushima Medical University, Faculty of Medicine, Dept. of Psychiatry, Professor, 医学部, 教授 (30110703)
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| Project Period (FY) |
2005 – 2006
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| Keywords | schizophrenia / monoamine / epigenetics / DNA methylation / post-mortem brain / MAOA / MAOB / nucleus accumbens |
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| Research Abstract |
It has been shown that most of monoamine-related genes are not correlated with susceptibility of schizophrenia, though dysfunctions of monoamine neuronal systems are well admitted to be related to pathogenesis of schizophrenia. Recent studies have shown that genes related to axonal elongation or development tend to significantly correlate with susceptibility of this disease. Thus, this made us to suspect if there are some epigenetic modulations on monoamine-related genes that express in the brain regions of schizophrenic patients. As epigenetics controls gene expression in the ontogenetic and cytodifferentiating process, but does not alter the information written in the genome.
In the present study, the methylation status of CpG islands in the promoter regions of MAOA and MAOB genes was examined, by using post-mortem brains of 6 cases with schizophrenia (3 males and 3 females, undifferentiated type : 4, paranoid type : 2, PMI : 7-26 hours) and 1 case with mental disorder, of Fukushima Psychiatric Brain Bank, and by bisulfite sequencing methods. Genome samples from brain tissues of four brain regions, the prefrontal cortex (BA 46), hippocampus, nucleus accumbens and occipital cortex, of each case were analyzed.
The DNA methylation status of MAOA and MAOB is successfully identified in brain tissue. In females, MAOA and MAOB showed moderate methylation, but not in males, presumably due to X-chromosome imprinting. The degrees of methylation of MAOA and MAOB did not differ significantly, with MAOA being slightly higher. The undifferentiated type seemed to show higher methylation of MAOA in the nucleus accumbens than other areas.
It is indicated that the DNA methylation status differs between sexes, brain regions examined, and subtypes of the disease. Further studies should be conducted to elucidate the significance of the DNA methylation in heterogeneity of pathogenesis of schizophrenia and its prognoses, using larger number of cases including controls.
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