Novel Mechanistic Links Between Trophic Factor Deprivation and Sensory Axon Degeneration

A recent paper in eNeuro from Phil Barker’s lab (University of British Columbia Okanagan, Canada) brings an unexpected finding in developmental mechanisms of axon degeneration. Neurotrophic support is needed for survival of many developing neuronal populations and plays a key role in defining neural circuits by regulating axon growth and maintenance. Loss of neurotrophic support causes axon degeneration and cultured embryonic neurons have long been used as a model for this developmental axon degeneration. Using cultures of rodent sensory neurons, Johnstone and colleagues show that as expected, removing nerve growth factor (NGF) results in axon degeneration. However, they surprisingly find that the capsaicin receptor, TRPV1 (Transient Receptor Potential Vanilloid family member 1), is involved in this degeneration. Further, Johnstone and colleagues show that NGF withdrawal leads to opening of the TRPV1 channel through a pathway requiring protein kinase C and NADPH oxidase activation and a consequent elevation of reactive oxygen species (ROS). This in turn causes ROS-dependent TRPV1 activation that allows influx of calcium ions and triggers axon degeneration (Figure 1). This novel role for TRPV1 in developmental axon degeneration and link to neurotrophic factor deprivation raises the possibility that TRPV1 activation could also contribute to axon degeneration in neurodegenerative diseases and in peripheral neuropathies.

Figure 1. TRPV1 mediates Ca2+ flux and cytoskeletal fragmentation during trophic factor deprivation. TRPV1-mediated Ca2+ flux is prompted by a signaling axis comprised of PKC-dependent NOX complex activation and ROS generation upstream of TRPV1 (Visual abstract from Johnstone et al. 2019).
Figure 1. TRPV1 mediates Ca2+ flux and cytoskeletal fragmentation during trophic factor deprivation. TRPV1-mediated Ca2+ flux is prompted by a signaling axis comprised of PKC-dependent NOX complex activation and ROS generation upstream of TRPV1 (Visual abstract from Johnstone et al. 2019).

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Developmental axon degeneration requires TRPV1-dependent Ca
Aaron D. Johnstone, Andrés de Léon, Nicolás Unsain, Julien Gibon and Philip A. Barker

Category: Editor's Pick
Tags: Neuroscience Research, Development