Developmental axon pruning mediated by BDNF-p75NTR–dependent axon degeneration

The mechanisms that regulate the pruning of mammalian axons are just now being elucidated. Here, we describe a mechanism by which, during developmental sympathetic axon competition, winning axons secrete brain-derived neurotrophic factor (BDNF) in an activity-dependent fashion, which binds to the p75 neurotrophin receptor (p75NTR) on losing axons to cause their degeneration and, ultimately, axon pruning. Specifically, we found that pruning of rat and mouse sympathetic axons that project to the eye requires both activity-dependent BDNF and p75NTR. p75NTR and BDNF are also essential for activity-dependent axon pruning in culture, where they mediate pruning by directly causing axon degeneration. p75NTR, which is enriched in losing axons, causes axonal degeneration by suppressing TrkA-mediated signaling that is essential for axonal maintenance. These data provide a mechanism that explains how active axons can eliminate less-active, competing axons during developmental pruning by directly promoting p75NTR-mediated axonal degeneration

Brain-Heart Communication Hardware and Software Strategies Through Nerves and Humoral Factors

none2noThe tight crosstalk between heart and brain is becoming increasingly recognized as the underlying mutual mechanisms are better identified, having a potential impact for clinical approach. Cardiac control is achieved bymeans of a three-level hierarchical neuronal network (central nervous system neurons, extracardiac-intrathoracic neurons, and intrinsic cardiac nervous system), where all the components work together to fulfill the physiological demands. However, each component of this network can undergo pathologic-mediated changes due to the transduction of altered sensory inputs originating from a deteriorating heart. A key role in the maintenance of cardiovascular homeostasis is played by the autonomic nervous system with its sympathetic and parasympathetic branches, which operate in a reciprocal manner. Heart rate best mirrors the relative balance between these two systems, and especially heart rate variability has emerged as a key parameter that reflects the health status of a given individual. Neural reflexes (i.e., the baroreceptor reflex) and several neuromodulators released from the heart itself or coming from other sites, as well as neurotrophins, also contribute to cardiovascular homeostasis and will be considered in the present chapter. A deeper understanding of heart-brain interactions will facilitate the prompt recognition and management of cardiac diseases, as well as of neurologic disorders associated to heart dysfunction, and, at the same time, will help in optimizing the therapeutic approach.mixedAlessia Pascale; Stefano GovoniPascale, ALESSIA ANGELA; Govoni, Stefan