Conditional genetic deletion of PTEN after a spinal cord injury enhances regenerative growth of CST axons and motor function recovery in mice

Exp Neurol, 2015 · DOI: 10.1016/j.expneurol.2015.02.012 · Published: April 1, 2015

Spinal Cord Injury Regenerative Medicine Rehabilitation

Simple Explanation

This study investigates whether deleting the PTEN gene in adult mice after a spinal cord injury can help the corticospinal tract (CST) axons regenerate. The study also assessed if this regeneration leads to enhanced recovery of voluntary motor function, specifically forelimb function. The researchers used a contusion injury model at the cervical level 5 (C5) in mice to simulate human spinal cord injuries and tested forelimb function using grip strength and hanging tasks.

Study Duration

14 weeks

Participants

38 adult female mice

Evidence Level

Not specified

Key Findings

1
PTEN deletion in adult mice shortly post-SCI can enhance regenerative growth of CST axons.
2
Mice with PTEN deletion showed significantly greater recovery in forelimb gripping ability compared to control groups.
3
BDA tract tracing revealed significantly higher numbers of BDA-labeled axons in caudal segments in the PTEN-deleted group compared to control groups.

Research Summary

The study demonstrated that conditional genetic deletion of PTEN in mature cortical motoneurons can enable regenerative growth of CST axons after SCI. Enhanced regeneration, achieved by deleting PTEN, improved forelimb gripping and grasping function in a clinically-relevant model (C5 contusion). The findings suggest that manipulations of PTEN or the downstream mTOR pathway may be a viable target for therapeutic interventions to promote axon regeneration after spinal cord injury.

Practical Implications

Therapeutic Target

PTEN and the mTOR pathway may be viable therapeutic targets for interventions to promote axon regeneration after spinal cord injury.

Clinical Relevance

The findings are clinically relevant because the study used a cervical contusion model, which mimics human spinal cord injuries, and showed improved forelimb motor function.

Timing of Intervention

Deleting PTEN in adult neurons shortly after injury can enhance regenerative growth, suggesting a potential therapeutic window for intervention.

Study Limitations

1
The extent of regenerative growth appears less extensive compared to previous studies where PTEN was deleted earlier.
2
It is an open question whether the GSM and hanging tasks can truly be called “voluntary” in the same sense as skilled manipulative tasks.
3
The laterality of control after PTEN deletion and injury is an assumption that could be disrupted by the bilateral extension of CST axons near the injury site.

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