Brain-derived neurotrophic factor protects against cardiac dysfunction after myocardial infarction via a central nervous system-mediated pathway

Sho Okada, Masataka Yokoyama, Haruhiro Toko, Kaoru Tateno, Junji Moriya, Ippei Shimizu, Aika Nojima, Takashi Ito, Yohko Yoshida, Yoshio Kobayashi, Hideki Katagiri, Tohru Minamino, Issei Komuro

Research output: Contribution to journalArticlepeer-review

100 Citations (Scopus)


Objective-The central nervous system is thought to influence the regulation of the cardiovascular system in response to humoral and neural signals from peripheral tissues, but our understanding of the molecular mechanisms involved is still quite limited. Methods and Results-Here, we demonstrate a central nervous system-mediated mechanism by which brain-derived neurotrophic factor (BDNF) has a protective effect against cardiac remodeling after myocardial infarction (MI). We generated conditional BDNF knockout mice, in which expression of BDNF was systemically reduced, by using the inducible Cre-loxP system. Two weeks after MI was induced surgically in these mice, systolic function was significantly impaired and cardiac size was markedly increased in conditional BDNF knockout mice compared with controls. Cardiomyocyte death was increased in these mice, along with decreased expression of survival molecules. Deletion of the BDNF receptor (tropomyosin-related kinase B) from the heart also led to the exacerbation of cardiac dysfunction after MI. The plasma levels of BDNF were markedly increased after MI, and this increase was associated with the upregulation of BDNF expression in the brain, but not in the heart. Ablation of afferent nerves from the heart or genetic disruption of neuronal BDNF expression inhibited the increase of plasma BDNF after MI and led to the exacerbation of cardiac dysfunction. Peripheral administration of BDNF significantly restored the cardiac phenotype of neuronal BDNF-deficient mice. Conclusion-These results suggest that BDNF expression is upregulated by neural signals from the heart after MI and then protects the myocardium against ischemic injury.

Original languageEnglish
Pages (from-to)1902-1909
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Issue number8
Publication statusPublished - 2012 Aug


  • angiogenesis
  • central nervous system
  • heart failure
  • myocardial infarction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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