Profiling sensory neuron microenvironment after peripheral and central axon injury reveals key pathways for neural repair

eLife, 2021 · DOI: https://doi.org/10.7554/eLife.68457 · Published: September 29, 2021

Neurology Regenerative Medicine & Stem Cells

Simple Explanation

Sensory neurons in dorsal root ganglia (DRG) are a useful model for studying axon regeneration. Axons regenerate after peripheral nerve injury, but not after spinal cord or dorsal root injury. The DRG microenvironment's influence on regenerative capacities after peripheral or central axon injury is largely unknown. The researchers performed single-cell transcriptional profiling of mouse DRG after peripheral and central axon injuries to address this question. Each cell type responded differently to the three injury types. All injuries increased a cell type sharing immune and glial cell features. A distinct subset of satellite glial cells (SGC) appeared specifically after peripheral nerve injury. Activation of the PPARα signaling pathway in SGC, which promotes axon regeneration after peripheral nerve injury, failed to occur after central axon injuries. Treatment with the PPARα agonist fenofibrate increased axon regeneration after dorsal root injury.

Study Duration

Not specified

Participants

Mice

Evidence Level

Not specified

Key Findings

1
Each cell type in the DRG microenvironment responds differently to peripheral (sciatic nerve crush), dorsal root crush, and spinal cord injuries.
2
Peripheral nerve injury induces a distinct subset of satellite glial cells (SGC) that are not observed after central axon injuries.
3
Activation of the PPARα signaling pathway in SGC, which promotes axon regeneration after peripheral nerve injury, fails to occur after central axon injuries; treatment with the PPARα agonist fenofibrate increased axon regeneration after dorsal root injury.

Research Summary

This study performed single-cell transcriptional profiling of mouse DRG in response to peripheral and central axon injuries. The study provides a map of the distinct DRG microenvironment responses to peripheral and central injuries at the single-cell level. The study highlights that manipulating non-neuronal cells could lead to avenues to promote functional recovery after CNS injuries or disease. The DRG microenvironment responds differently to central and peripheral axon injuries. Treatment with the FDA-approved PPARα agonist fenofibrate increased axon regeneration after dorsal root injury. This indicates that the DRG microenvironment responds differently to central and peripheral axon injuries.

Practical Implications

Drug development

The study suggests that targeting non-neuronal cells in the DRG could lead to new therapeutic strategies for promoting functional recovery after CNS injuries or disease.

Personalized medicine

Understanding the distinct responses of different cell types in the DRG microenvironment to different types of injuries could lead to more personalized treatment approaches.

Clinical trials

The study provides a rationale for further investigation of fenofibrate, an FDA-approved PPARα agonist, as a potential therapeutic for promoting axon regeneration after dorsal root injury.

Study Limitations

1
The study focused on acute injuries; the long-term effects of these injuries on the DRG microenvironment are unknown.
2
The study used a mouse model; the findings may not be directly translatable to humans.
3
The study only examined a limited number of cell types in the DRG microenvironment; other cell types may also play a role in axon regeneration.

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