BDNF Actions in the Cardiovascular System: Roles in Development, Adulthood and Response to Injury

This study also identified the cardiac myocyte as a significant local source of BDNF, as cardiac myocyte-specific deletion of BDNF induced a similar cardiomyopathy phenotype. While these results do not exclude a role for other neurotrophins, particularly in injury states, they point to the requirement for continued, local synthesis of BDNF to maintain optimal cardiac function. A major, unresolved question relates to how the truncated TrkB isoform (TrkBT1) transduces the inotropic effects of BDNF, which will require additional study. A concurrent study evaluated the potential impact of the BDNF-mediated activation of the kinase active isoform of TrkB in the adult heart, by genetically deleting this isoform in cardiac myocytes (Feng et al., 2014). Using this approach, deficits in CaMKII activity were observed upon deletion of kinase active TrkB. While deficits in systolic function were observed, these were not significant enough to trigger chamber dilation or reduce ejection fraction. Interestingly, in models of cardiac failure (induced by transverse aortic constriction, or in hearts overexpressing G α q that display cardiac dilation), induction of the truncated isoform (TrkBT1) is observed, suggesting a compensatory mechanism to augment myocyte contractility (Figure 1). These studies are highly relevant as the field considers the use of BDNF-mimetics to enhance TrkB activation in central neurons for the treatment of mood disorders, regulation of food intake, and neuro...
Source: Frontiers in Physiology - Category: Physiology Source Type: research