title: Brain-derived neurotrophic factor protects against cardiac dysfunction after myocardial infarction via a central nervous system-mediated pathway.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  These results suggest that BDNF expression is upregulated by neural signals from the heart after MI and then protects the myocardium against ischemic injury.
authors.affiliation: Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Okada
authors.forename: Masataka
authors.initials: M
authors.lastname: Yokoyama
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Toko
authors.forename: Kaoru
authors.initials: K
authors.lastname: Tateno
authors.forename: Junji
authors.initials: J
authors.lastname: Moriya
authors.forename: Ippei
authors.initials: I
authors.lastname: Shimizu
authors.forename: Aika
authors.initials: A
authors.lastname: Nojima
authors.forename: Takashi
authors.initials: T
authors.lastname: Ito
authors.forename: Yohko
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Hideki
authors.initials: H
authors.lastname: Katagiri
authors.forename: Tohru
authors.initials: T
authors.lastname: Minamino
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000503:physiopathology*; D020813:Receptor, trkB / Q000502:physiology; D015398:Signal Transduction; D013599:Systole; D020257:Ventricular Remodeling
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB