Pten Deletion Promotes Regrowth of Corticospinal Tract Axons 1 Year after Spinal Cord Injury

The Journal of Neuroscience, 2015 · DOI: 10.1523/JNEUROSCI.3637-14.2015 · Published: July 1, 2015

Spinal Cord Injury Neurology Regenerative Medicine & Stem Cells

Simple Explanation

This study investigates promoting axon regeneration after chronic spinal cord injury (SCI), focusing on the corticospinal tract (CST). The researchers modulated Pten/mammalian target of rapamycin signaling in adult corticospinal motor neurons. The study found that this modulation not only promoted sprouting of uninjured CST axons but also enabled regeneration of injured axons past the lesion. Importantly, these effects were observed even when the treatment was delayed up to 1 year after the initial injury, suggesting a longer window of opportunity for regenerating CST axons severed in spinal cord injuries.

Study Duration

19 Months

Participants

Mice

Evidence Level

Not specified

Key Findings

1
Pten deletion in adult mice promotes CST sprouting after unilateral pyramidotomy, as demonstrated by BDA tracing.
2
Pten deletion initiated 4 weeks after T8 crush induces CST regeneration.
3
Treatment delayed for 12 months promotes CST axon regeneration in a chronic injury model.

Research Summary

This study demonstrates that Pten deletion in postinjured adult corticospinal neurons enables a regenerative response in the mammalian spinal cord. Both the compensatory sprouting of intact CST axons and the regenerative growth of injured CST axons were significantly increased by Pten deletion. Pten deletion in both mature and injured neurons could reverse the mTOR downregulation, and promote the regrowth ability.

Practical Implications

Extending Therapeutic Window

The study considerably extends the window of opportunity for regenerating CST axons severed in spinal cord injuries, suggesting potential for treatments even long after the initial injury.

Targeting mTOR Pathway

Modulating neuronal mTOR activity emerges as a potential strategy for axon regeneration after chronic SCI, offering a new avenue for therapeutic interventions.

Understanding Chronic Injury Response

The research sheds light on the sustained injury signal that triggers axon growth, providing valuable insights into the mechanisms underlying chronic SCI and potential targets for therapeutic manipulation.

Study Limitations

1
The functional outcome of the regenerated CST axons remains to be tested.
2
The identity and function of the progenitor-like cells need to be further investigated.
3
The regeneration was mild.

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