| Project/Area Number |
23300145
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurophysiology and muscle physiology
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| Research Institution | Kyushu University |
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Principal Investigator |
MORIMOTO Sachio 九州大学, 医学(系)研究科(研究院), 准教授 (50202362)
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| Co-Investigator(Renkei-kenkyūsha) |
KATAFUCHI Toshihiko 九州大学, 大学院・医学研究院, 准教授 (80177401)
TAKE Sachiko 九州大学, 大学院・医学研究院, 助教 (80253425)
KUREBAYASHI Nagomi 順天堂大学, 医学部, 准教授 (50133335)
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| Project Period (FY) |
2011-11-18 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
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| Keywords | うっ血性心不全 / うつ病 / 不安障害 / 脳 / セロトニン / トリプトファン / 遺伝的要因 / 拡張型心筋症 / 心不全 / 抗うつ薬 / 抗不安薬 / ノックインマウス / 迷走神経 |
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| Research Abstract |
In this study, we explored the role of brain serotonin function in the development of congestive heart failure (HF), using knock-in mice bearing a sarcomeric protein mutation that causes dilated cardiomyopathy (DCM) on different genetic backgrounds; BALB/c and C57Bl/6. BALB/c background mice, which have brain serotonin dysfunction due to a single nucleotide polymorphism in tryptophan hydroxylase 2, developed congestive HF before died. In contrast, C57Bl/6 background mice with normal brain serotonin function developed no overt HF symptoms and died suddenly. Brain serotonin dysfunction plays a critical role in depression and anxiety and BALB/c mice exhibit depression- and anxiety-related behaviors. Drugs that could improve the brain serotonin function improved symptoms of severe congestive HF in DCM mice on the BALB/c background. These results strongly suggest that congenital or acquired brain serotonin dysfunction may play an important role in the development of congestive HF in DCM.
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