Establishment of therapeutic approach to chronic heart failure focusing on brain-heart interaction

• Project/Area Number: 16K09506
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Fukushima Medical University
• Principal Investigator: Oikawa Masayoshi 福島県立医科大学, 医学部, 助教 (30457775)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 交感神経 / 慢性心不全 / 星状神経節 / 脊髄中間外側核 / 脳心連関 / 交感神経リモデリング / 神経リモデリング / 心筋梗塞

Outline of Final Research Achievements

The purpose of this study was to examine whether MI induces neuronal remodeling of intermediolateral nucleus (IML). Myocardial infarction (MI) was induced in a rat model. Neural remodeling in the IML and stellate ganglia (SG) was assessed by immunohistochemistry 2 weeks after MI. Results: The neuronal size in SG were enlarged after MI compared to sham. The choline acetyltransferase-immunoreactive neuronal size and axonal density in IML were increased after MI compared to sham. mRNA expression of brain-derived neural factor (BDNF) and TrkB in the spinal cord was increased after MI, suggesting that BDNF-TrkB axis plays pivotal roles in the neural remodeling in IML.The increased ratio of phospho-ERK/total ERK at the corresponding level of spinal cord in MI group assessed by Western blotting. These data suggest that increased expressions of the BDNF-TrkB axis in IML lead to ERK activation with resultant neuronal hypertrophy of IML and sprouting into SG after MI.

Academic Significance and Societal Importance of the Research Achievements

交感神経リモデリング現象、特に中枢神経系における心不全と交感神経リモデリングについての検討はこれまで行われていなかった。本研究は心不全状態が星状神経節の上流である脊髄中間外側核においても神経リモデリングを呈していることを示した。本所見は、心不全状態における中枢系交感神経過剰活性の組織学的新知見であり、今後増加が予想されている慢性心不全病態における中枢神経の関与を解明する基礎データとなる。

Research Products

• [Journal Article] Sympathetic nervous remodeling is induced in the intermediolateral nucleus after myocardial infarction ? Role of BDNF-TrkB axis- (2018)
  • Author(s): Nodera Minoru、Oikawa Masayoshi、Nakazato Kazuhiko、Ishida Takafumi、Takeishi Yasuchika
  • Journal Title: Neuroscience Letters Volume: 685 Pages: 114-123
  • DOI: 10.1016/j.neulet.2018.08.004
  • Peer Reviewed
• [Presentation] Sympathetic Nervous Remodeling in Intermediolateral Nuclei Is Induced after Myocardial Infarction via Activation of BDNF-TrkB Axis (2018)
  • Author(s): 野寺穣 及川雅啓 石田隆史 竹石恭知
  • Organizer: 国際心臓研究会日本部会
• [Presentation] Sympathetic Nervous Remodeling in Intermediolateral Nuclei Is Induced after Myocardial Infarction via Activation of BDNF-TrkB Axis (2018)
  • Author(s): 野寺穣 及川雅啓 石田隆史 竹石恭知
  • Organizer: ヨーロッパ心臓病学会
  • Int'l Joint Research
• [Presentation] Sympathetic Remodeling in Intermediolateral Nuclei after Myocardial Infarction via BDNF-TrkB Axis (2018)
  • Author(s): 野寺 穣
  • Organizer: 1st JCS Council Forum on Basic CardioVascular Research
  • Int'l Joint Research
• [Presentation] Phosphodiesterase 3A1 Prevents Cardiac Remodeling from Neurohormonal Activation (2016)
  • Author(s): 及川雅啓
  • Organizer: 2016年国際心臓研究会
  • Place of Presentation: ブエノスアイレス アルゼンチン
  • Year and Date: 2016-04-20
  • Int'l Joint Research