2020 Fiscal Year Final Research Report
Significance of MAOB in paraventricular nucleus-specific mitochondrial defects that relevant to a cause of mood disorders
| Project/Area Number |
18K07615
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 52030:Psychiatry-related
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| Research Institution | Institute of Physical and Chemical Research |
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Principal Investigator |
Kubota-Sakashita Mie (坂下美恵) 国立研究開発法人理化学研究所, 脳神経科学研究センター, 客員研究員 (90344035)
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| Co-Investigator(Kenkyū-buntansha) |
島 康之 国立研究開発法人理化学研究所, 脳神経科学研究センター, 上級研究員 (60815885)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | モノアミンオキシダーゼB / 気分障害 / フェニルエチルアミン / 稀少アミン / ミトコンドリア |
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| Outline of Final Research Achievements |
To investigate substrates of monoamine oxidase b (Maob) in brain, we developed Maob knockout (KO) mice and Maob flox/flox mice by CRISPR/Cas9 system and measured amounts of monoamines and their metabolites by LC-MS/MS. Noradrenaline, dopamine, 3-methoxytyramine, phenylethylamine (PEA), serotonin, and 5-hidroxyindoleacetic acid was detected in eight brain regions including paraventricular thalamus (PVT). To evaluate the expression level of Maob, qPCR method by SYBR green was applied to quantify the expression. We measured expression level of Maoa and NDP genes which locate on the same chromosome as Maob. Maob gene expression was markedly decreased and Maoa and NDP genes was not, suggesting that specific KO of Maob was succeeded. Further, we tried imaging mass spectrometry of monoamines using frozen section of the brain. Although signals of serotonin, noradrenaline, dopamine were detected, improved methods such as derivatization should be applied for an accurate quantification.
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| Free Research Field |
神経科学
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| Academic Significance and Societal Importance of the Research Achievements |
現在、モノアミン神経伝達の機能不全は多くの神経・精神障害を引き起こすと考えられている。脳内モノアミン濃度は、モノアミン酸化酵素（Mao）によって調節されうるが、その一つであるMaobは、脳内では視床室傍核（PVT）および背側縫線核に高発現している。PVTは、感情的な行動に関与する脳領域と、機能的および解剖学的に関連しており、PVTにおけるMaob の基質を探索することが重要である。
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