| Project/Area Number |
17K14965
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | Tohoku Medical and Pharmaceutical University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | ヒスタミン / 条件的遺伝子欠損 / AAVベクター / AAV / 脳内ヒスタミン / 条件的遺伝子欠損法 / アデノ随伴ウイルス / 脳内微量注入法 |
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| Outline of Final Research Achievements |
Microinjection of AAV-Cre into brain regions of Hnmt (a histamine-metabolizing enzyme)-flox mice increased histamine concentration in the injected regions. Increased histamine in hypothalamus increased locomotor activity, whereas that in amygdala increased aggression behaviors, respectively. On the other hand, in Hdc (histamine synthetase)-flox mice, microinjection of AAV-Cre into hypothalamus decreased brain histamine and induced the anxiety-like behaviors and suppressed locomotor activity and aggression behaviors. These results showed that histaminergic neurons were important for locomotor activity in hypothalamus and aggression behaviors in amygdala, suggesting that histaminergic neurons have a different role in various brain regions. In addition, this study could develop the new methods to study each functions of brain histamine depend on each brain regions.
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| Academic Significance and Societal Importance of the Research Achievements |
従来の中枢ヒスタミン研究では、主にノックアウトマウスを用いた研究が行われてきたが、代償性機構が無視できなかった。しかしながら、本研究で確立したAAV微量注入法では、成体マウスで遺伝子操作を行うため、代償性機構をある程度無視出来る。さらに、ヒスタミン神経系の役割を脳部位毎に、gain-of-functionまたはloss-of-function両面から検討できる。本研究で確立した方法により脳部位別のヒスタミン神経系の役割がさらに明らかとなれば、疾病によって脳部位ごとに様々な神経活動の異常が認められるヒスタミン神経系が、それぞれの病態にどのように影響を与えているのか明確に出来ると期待される。
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