PTEN Deletion Enhances the Regenerative Ability of Adult Corticospinal Neurons

Nat Neurosci, 2010 · DOI: 10.1038/nn.2603 · Published: September 1, 2010

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

The corticospinal tract (CST) is crucial for voluntary movement, but it doesn't regenerate well after spinal cord injury. This study found that a protein called PTEN and a pathway called mTOR are involved in the ability of CST axons to regrow. Researchers deleted PTEN, which normally inhibits mTOR, in mice. This increased mTOR activity and significantly improved the regrowth of injured CST axons past spinal cord lesions. These regrown axons could even form new connections (synapses) in the spinal cord, suggesting a potential way to repair the spinal cord after injury by manipulating the PTEN/mTOR pathway.

Study Duration

6-18 Weeks

Participants

Mice

Evidence Level

Not specified

Key Findings

1
Deleting PTEN in adult corticospinal neurons enhances compensatory sprouting of uninjured CST axons.
2
PTEN deletion enables successful regeneration of injured CST axons past a spinal cord lesion.
3
Regenerating CST axons can reform synapses in spinal segments distal to the injury.

Research Summary

This study investigates the role of PTEN/mTOR in controlling the regenerative capacity of mouse corticospinal neurons after spinal cord injury. The researchers found that forced up-regulation of mTOR activity by conditional deletion of PTEN enhances sprouting of uninjured CST axons and enables regeneration of injured CST axons. The study concludes that modulating neuronal intrinsic PTEN/mTOR activity represents a potential therapeutic strategy for promoting axon regeneration and functional repair after adult spinal cord injury.

Practical Implications

Therapeutic Target

PTEN/mTOR pathway modulation could be a therapeutic target for spinal cord injury.

Rejuvenation Strategy

Re-activation of mTOR pathway can allow adult neurons to regain growth capacities.

Combination Therapy

Combining PTEN deletion with other strategies may further promote maximal axon regeneration.

Study Limitations

1
Many robustly growing axons fail to penetrate into the GFAP-negative area at the lesion site.
2
Regenerating CST axons extend bilaterally, unlike the unilateral projection of normal CST axons.
3
Whether the reformed synapses are functional and the identity of the contacted neurons needs to be established.

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