α9 Integrin Promotes Neurite Outgrowth on Tenascin-C and Enhances Sensory Axon Regeneration

The Journal of Neuroscience, 2009 · DOI: 10.1523/JNEUROSCI.0759-09.2009 · Published: April 29, 2009

Regenerative Medicine Neurology Genetics

Simple Explanation

Damaged nerve fibers in the central nervous system (CNS) struggle to regenerate due to inhibitory factors in their environment. This study explores whether introducing a specific integrin, α9β1, can help these fibers regenerate by interacting with tenascin-C, a protein abundant after CNS injury. The researchers found that by forcing cells and nerve fibers to express α9 integrin, they could promote significant neurite outgrowth on tenascin-C in lab settings. This suggests α9 integrin can help nerve cells grow on tenascin-C, which is usually not a supportive environment. In live rats, after spinal cord injuries, expressing α9 integrin led to more nerve fibers regrowing into the damaged areas. Also, the rats treated with α9 integrin showed signs of regaining normal sensation, indicating improved nerve function after the injury.

Study Duration

6 weeks

Participants

Adult male Sprague Dawley rats or adult C57BL/6 mice

Evidence Level

In vitro and in vivo study

Key Findings

1
Expression of α9 integrin in PC12 cells and adult rat DRG neurons promotes extensive neurite outgrowth on tenascin-C in vitro.
2
DRG neurons and PC12 cells secrete tenascin-C, enabling α9-transfected cells to grow axons on tissue culture plastic.
3
In vivo expression of α9 integrin in DRGs enhances axonal regeneration after cervical dorsal rhizotomy and dorsal column crush in adult rats.

Research Summary

This study demonstrates that α9 integrin expression promotes neurite outgrowth on tenascin-C (TN-C) both in vitro and in vivo, suggesting a potential therapeutic strategy for enhancing axon regeneration in the damaged CNS. In vitro experiments showed that α9 integrin expression in PC12 cells and adult DRG neurons significantly enhanced neurite outgrowth on TN-C, and that these cells secrete TN-C, allowing α9-transfected cells to grow on tissue culture plastic. In vivo studies using adeno-associated viruses to express α9 integrin in DRGs of adult rats revealed increased axonal regeneration into the dorsal root entry zone after rhizotomy and into the lesion site after a dorsal column crush injury, along with some functional recovery.

Practical Implications

Therapeutic Potential

Gene therapy targeting integrin expression could be a strategy to promote axon regeneration after CNS injuries.

Understanding Integrin Signaling

Further research into integrin activation and trafficking mechanisms is warranted to optimize the effectiveness of integrin-based therapies.

Combination Therapies

Combining integrin manipulation with other strategies, like chondroitinase treatment or cell transplantation, might have additive effects on CNS repair.

Study Limitations

1
The extent of axon regeneration in vivo was less extensive than observed in vitro.
2
The study lacks reliable antibodies for immunohistochemical localization of α9 integrin, relying on co-expression of GFP.
3
Potential influences from other inhibitory molecules in vivo, such as NogoA and chondroitin sulfate proteoglycans, may affect integrin activation.

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