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  3. Regenerative Medicine
  4. Functional Regeneration of the Sensory Root via Axonal Invasion

Functional Regeneration of the Sensory Root via Axonal Invasion

Cell Reports, 2020 · DOI: 10.1016/j.celrep.2019.12.008 · Published: January 7, 2020

Regenerative MedicineNeurologyGenetics

Simple Explanation

Following spinal root injuries, unlike other peripheral nerves, the sensory axons from DRG neurons fail to regenerate back into the spinal cord. This study found that DRG neurons do not properly re-enter the spinal cord because, after injury, they fail to initiate actin-based invasion. The study used a zebrafish model to examine DRG axon regeneration following laser-induced injury. Researchers discovered that by using pharmacological (Taxol) and cell-autonomous genetic manipulations (CA-Src) to promote actin-mediated cell invasion, they could restore sensory behavior in the zebrafish model. Taxol stabilizes invasion components to drive spinal cord re-entry following injury. The study demonstrates that by stimulating axons to re-enter the spinal cord via invasion, it's possible to achieve functional sensory root regeneration after injury. They demonstrated restoration of sensory circuit activity and behavior upon stimulating axons to re-enter the spinal cord via invasion.

Study Duration
24 hours post-injury
Participants
Zebrafish embryos (2-5 dpf)
Evidence Level
In vivo experimental study in zebrafish

Key Findings

  • 1
    Regenerating DRG sensory axons do not initiate actin-based invasion components during re-entry into the spinal cord following avulsion-like injuries.
  • 2
    Pharmacological stabilization of invasion components with Taxol promotes DRG axon spinal re-entry after injury, suggesting that stabilizing these components can rescue regeneration.
  • 3
    Cell-autonomous induction of invasion components using constitutively active Src (CA-Src) in DRG cells drives invasion and promotes axonal regeneration, indicating an intrinsic mechanism can be activated to drive regeneration.

Research Summary

This study investigates why regeneration following spinal root avulsion is broadly unsuccessful. It identifies that regenerating DRG neurons fail to recapitulate developmental paradigms of actin-based invasion after injury. The research demonstrates that inducing actin reorganization into invasive components via pharmacological and genetic approaches in the regenerating axon can rescue sensory axon spinal cord entry. Analyses of neuronal activity and animal behavior show restoration of sensory circuit activity and behavior upon stimulating axons to re-enter the spinal cord via invasion.

Practical Implications

Therapeutic Potential

Targeting actin-mediated invasion may offer a novel therapeutic avenue for promoting sensory root regeneration after avulsion injuries.

Understanding Regeneration

The study provides insights into the mechanisms underlying failed regeneration in the central nervous system.

Cell Invasion Mechanism

The work illuminates the role of cell invasion machinery in overcoming physical limits to axonal regrowth.

Study Limitations

  • 1
    The study is performed on zebrafish; translation to humans requires further research.
  • 2
    The study focuses on early recovery (1-2 days post injury).
  • 3
    The study only assesses partial behavioral and circuit recovery.

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