Reinduced Wnt signaling limits regenerative potential of sensory axons in the spinal cord following conditioning lesion

PNAS, 2012 · DOI: 10.1073/pnas.1206218109 · Published: September 4, 2012

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Peripheral conditioning lesion, a technique used to stimulate nerve regeneration after spinal cord injury, induces both growth-promoting and growth-inhibiting factors. This study found that Wnt signaling, specifically through the Ryk receptor, inhibits the regeneration of sensory axons in the spinal cord after a conditioning lesion. Blocking Wnt signaling with specific inhibitors enhanced axon regeneration, while promoting Wnt signaling caused axons to retract, suggesting that overcoming Wnt inhibition may improve therapies for spinal cord injuries.

Study Duration

Not specified

Participants

Adult female Fischer 344 rats

Evidence Level

Not specified

Key Findings

1
Peripheral conditioning injury induces the expression of the repulsive Wnt receptor Ryk in sensory neurons.
2
Blocking Wnt signaling with Wnt inhibitors (SFRP2 and WIF1) enhanced the regeneration of conditioned dorsal column axons.
3
Grafting cells that overexpress Wnt4 resulted in long-range retraction of conditioned dorsal column axons.

Research Summary

This study investigates the role of Wnt signaling in limiting the regenerative potential of sensory axons in the spinal cord following a conditioning lesion. The research demonstrates that blocking Wnt signaling enhances axon regeneration, while Wnt4 overexpression causes axon retraction, suggesting that Wnt-Ryk signaling inhibits regeneration. The findings suggest that overcoming Wnt inhibition could improve spinal cord injury therapies based on the conditioning lesion paradigm.

Practical Implications

Therapeutic Target

Wnt-Ryk signaling pathway is a potential therapeutic target for promoting axon regeneration after spinal cord injury.

Combination Therapy

Combining Wnt inhibition with conditioning lesion approaches may lead to greater regeneration and functional recovery.

Further Research

Further investigation is needed to understand the potential roles of Wnts in other CNS injury responses.

Study Limitations

1
Only a handful of axons were found to bridge beyond the lesion site with Wnt inhibition.
2
Additional inhibition, such as that mediated by myelin-associated inhibitors or chondroitin sulfate proteoglycans, may need to be removed.
3
The intrinsic growth potential will need to be further enhanced via combinatorial approaches to achieve greater regeneration and functional recovery.

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