Netrin-1 Is a Novel Myelin-Associated Inhibitor to Axon Growth

The Journal of Neuroscience, 2008 · DOI: 10.1523/JNEUROSCI.4906-07.2008 · Published: January 30, 2008

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Netrin-1, a molecule known for guiding axons, is found on mature oligodendrocytes in the adult spinal cord. These cells also produce other inhibitors like Nogo, MAG, and OMgp. This study explores whether netrin-1 affects axonal growth after spinal cord injury. The study found that neurons which project to the spinal cord, express receptors for netrin-1 called UNC5. By neutralizing netrin-1 in myelin extracts, the researchers observed increased neurite outgrowth from these neurons in vitro. In spinal cord injury models, blocking netrin-1 in areas of injury promoted axon regeneration. This suggests that netrin-1 acts as an inhibitor of axonal regeneration in the injured adult spinal cord.

Study Duration

5 weeks and 3 months

Participants

Adult female Fisher rats (160–200 g)

Evidence Level

Not specified

Key Findings

1
Netrin-1 is expressed by mature oligodendrocytes in the adult spinal cord and is enriched near paranodal loops in nodes of Ranvier.
2
Neurons of the corticospinal and rubrospinal projections, as well as intrinsic spinal cord neurons, express UNC5 receptors for netrin-1, both before and after spinal cord injury.
3
Neutralizing netrin-1 in adult myelin extracts increases neurite outgrowth from UNC5-expressing spinal motor neurons in vitro.

Research Summary

This study identifies netrin-1 as a novel oligodendrocyte-associated inhibitor of axonal growth in the adult spinal cord. Netrin-1 and its receptors are expressed in the intact and lesioned adult CNS. Netrin-1 is enriched near paranodal loops at nodes of Ranvier. Axonal growth is inhibited in a zone containing netrin-1 that is devoid of other myelin-associated inhibitors in in vivo sites of spinal cord injury.

Practical Implications

Targeted Therapies

Developing therapies that specifically target and neutralize netrin-1 could promote axonal regeneration after spinal cord injury.

Combination Therapies

Combining netrin-1 neutralization with other strategies that promote axonal growth may lead to enhanced recovery after spinal cord injury.

Understanding Myelin Inhibition

Further research into the mechanisms by which netrin-1 inhibits axonal growth could reveal new targets for therapeutic intervention.

Study Limitations

1
The study focuses primarily on netrin-1's role as an inhibitor, potentially overlooking its attractive properties during development or in specific contexts.
2
The in vivo experiments involve overexpressing netrin-1 in fibroblasts, which may not fully replicate the natural expression patterns and interactions in the spinal cord.
3
The study uses a rat model of spinal cord injury, and the findings may not directly translate to humans.

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