Functions of central histaminergic neurons in pathological model

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K14965
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Tohoku Medical and Pharmaceutical University
• Principal Investigator: NAGANUMA Fumito 東北医科薬科大学, 医学部, 助教 (80780519)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: ヒスタミン / 条件的遺伝子欠損 / AAVベクター

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.

Free Research Field

神経薬理学

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。