Adult rat myelin enhances axonal outgrowth from neural stem cells

Sci Transl Med, 2018 · DOI: 10.1126/scitranslmed.aal2563 · Published: May 23, 2018

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates how myelin, a substance that usually inhibits nerve growth after spinal cord injury, affects the growth of new nerve cells from stem cells. The researchers found that, surprisingly, myelin stimulated the growth of axons (nerve fibers) from neural stem cells, both in lab dishes and in rats with spinal cord injuries. They identified a protein called Negr1 that helps mediate this growth-promoting effect, suggesting a potential new way to encourage nerve regeneration after spinal cord injury.

Study Duration

2 weeks to 3 months

Participants

38 rats and 18 mice

Evidence Level

Not specified

Key Findings

1
Adult rat myelin stimulated the growth of axons emerging from rat neural progenitor cells (NPCs) transplanted into sites of SCI in adult rat recipients.
2
NPC-derived axons preferentially extended through adult host white matter in vivo and preferentially associate with host myelin in vivo.
3
Myelin extracts directly activate neuron-intrinsic growth programs, and Negr1 mediates neurite growth on a myelin substrate in rat NPCs.

Research Summary

This study challenges the conventional understanding of myelin's role in nerve regeneration after spinal cord injury (SCI). The findings demonstrate that adult rat myelin unexpectedly enhances axonal outgrowth from neural stem cells (NSCs), both in vitro and in vivo. The identification of Negr1 as a key mediator of this growth-promoting effect provides a potential target for developing new strategies to promote nerve regeneration and functional recovery after SCI.

Practical Implications

Therapeutic Target

Negr1 could be targeted to enhance axon regeneration after SCI.

Stem Cell Therapy

NPC-based therapies show promise for neural repair.

Drug Development

Fractionation of myelin extract could lead to therapeutic compounds to promote axon growth.

Study Limitations

1
Other candidates identified by RNA-seq should be investigated to probe contributions of other molecules to myelin-mediated growth.
2
The total myelin extract used in our work might be more representative of myelin debris that is exposed at the lesion site rather than intact or degenerating myelin found in the spinal cord white matter rostral and caudal to the lesion.
3
It will be of interest to identify the molecules within adult CNS myelin extract that promote axon growth.

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