Sympathetic nervous remodeling is induced in the intermediolateral nucleus after myocardial infarction - Role of BDNF-TrkB axis

Abstract

Several studies have shown that neural remodeling in stellate ganglia (SG) is induced by myocardial infarction (MI). It remains unclear whether neural remodeling after MI is limited in SG within the sympathetic nervous system (SNS). MI was induced in a rat model by ligation of the left anterior descending artery. Neural remodeling in the intermediolateral nucleus (IML) and 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 density of growth-associated protein-43, a protein upregulated in axons undergoing nerve sprouting, was 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. In conclusion, neural remodeling after MI in IML is associated with the activation of BDNF-TrkB axis. Morphological remodeling throughout the SNS may be involved in sustained activation of sympathetic tone after MI.

Keywords: Brain-derived neurotrophic factor; Intermediolateral nucleus; Myocardial infarction; Neural remodeling; Tropomyosin-related kinase receptor B.