Preconditioning nerve injuries activate a pro-regenerative program that enhances axon regeneration for most classes of sensory neurons. However, nociceptive sensory neurons and central nervous system neurons regenerate poorly. In hopes of identifying novel mechanisms that promote regeneration, we screened for drugs that mimicked the preconditioning response and identified a nociceptive ligand that activates a preconditioning-like response to promote axon outgrowth. We show that activating the ion channel TRPV1 with capsaicin induces axon outgrowth of cultured dorsal root ganglion (DRG) sensory neurons, and that this effect is blocked in TRPV1 knockout neurons. Regeneration occurs only in NF200-negative nociceptive neurons, consistent with a cell-autonomous mechanism. Moreover, we identify a signaling pathway in which TRPV1 activation leads to calcium influx and protein kinase A (PKA) activation to induce a preconditioning-like response. Finally, capsaicin administration to the mouse sciatic nerve activates a similar preconditioning-like response and induces enhanced axonal outgrowth, indicating that this pathway can be induced in vivo. These findings highlight the use of local ligands to induce regeneration and suggest that it may be possible to target selective neuronal populations for repair, including cell types that often fail to regenerate.
Pubmed ID: 29854941 RIS Download
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View all literature mentionsThis polyclonal secondary targets Rabbit IgG (H+L)
View all literature mentionsThis unknown targets Neurofilament 200
View all literature mentionsThis monoclonal targets Phospho-CREB (Ser133)
View all literature mentionsThis monoclonal targets Neuronal Class III beta-Tubulin (TUJ1) Purified
View all literature mentionsSoftware tool to enable biologists without training in computer vision or programming to quantitatively measure phenotypes from thousands of images automatically. It counts cells and also measures the size, shape, intensity and texture of every cell (and every labeled subcellular compartment) in every image. It was designed for high throughput screening but can perform automated image analysis for images from time-lapse movies and low-throughput experiments. CellProfiler has an increasing number of algorithms to identify and measure properties of neuronal cell types.
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View all literature mentionsThis polyclonal secondary targets Rabbit IgG (H+L)
View all literature mentionsThis unknown targets Neurofilament 200
View all literature mentionsThis monoclonal targets Phospho-CREB (Ser133)
View all literature mentionsThis monoclonal targets Neuronal Class III beta-Tubulin (TUJ1) Purified
View all literature mentions