Brain-Derived Neurotrophic Factor Protects Against Cardiac Dysfunction After Myocardial Infarction via a Central Nervous System–Mediated Pathway

• DOI: 10.1161/atvbaha.112.248930
• Publication Date: 2012-05-04T05:52:27Z
• Authors: 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
• Keywords: Knockout mouse

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