Construction of Heart Failure Treatment Strategy by Sympathetic Neural Remodeling -From the Viewpoint of Brain-Heart Connection-
| Project/Area Number |
18K15854
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53020:Cardiology-related
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| Research Institution | University of Fukui (2019)
Fukushima Medical University (2018) |
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Principal Investigator |
Nodera Minoru 福井大学, 学術研究院医学系部門(附属病院部), 助教 (40769593)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | Neural remodeling / 心筋梗塞 / 脊髄中間外側核 / BDNF / TrkB / IML / neural remodeling / 交感神経 / 心不全 / NeuRetベクター / 神経栄養因子 |
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| Outline of Final Research Achievements |
Myocardial infarction (MI) was induced in a rat model by ligation of the left anterior descending artery. Neural remodeling in the intermediolateral nucleus (IML) and stellate ganglia (SG) was assessed by immunohistochemistry 2 weeks after MI. The mRNA and protein expressions of brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase receptor (TrkB) and extracellular signal-regulated kinase (ERK) were measured by quantitative RT-PCR, immunohistochemistry and Western blotting 1 week after MI. The neuronal size and axonal density of IML were increased after MI compared to sham. The fluorescence intensity of BDNF and TrkB in IML were significantly higher in the MI group than in the sham group. In addition, mRNA expressions of BDNF and TrkB in the spinal cord at the Th2 level was increased after MI. Finally, the percentage of phospho-ERK-immunoreactive cells in IML was significantly higher in the MI group than in the sham group.
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| Academic Significance and Societal Importance of the Research Achievements |
心筋梗塞後の交感神経活性亢進にはSGのneural remodelingが関与していると考えられている。この現象が交感神経系においてSGのみならず他の部位でも認められるのかは明らかにはされていない。本研究では心筋梗塞後においてはIMLも neural remodelingをきたし、それにはBDNF/TrkB経路の活性化が関与していることが示唆された。心筋梗塞後、交感神経系全体において神経リモデリング現象が生じ、それが更なる交感神経緊張を引き起こしている可能性がある。本研究は心筋梗塞を始めとする慢性心不全患者における交感神経過剰活性の抑制という新たな治療法を確立する基盤になると考えられる。
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Report
(3 results)
Research Products
(2 results)
