Identification of Intrinsic Axon Growth Modulators for Intact CNS Neurons after Injury

Cell Rep, 2017 · DOI: 10.1016/j.celrep.2017.02.058 · Published: March 14, 2017

Spinal Cord Injury Regenerative Medicine Bioinformatics

Simple Explanation

After spinal cord injury, the central nervous system's axons fail to regenerate, leading to lasting functional issues. However, some natural recovery occurs due to the brain's ability to adapt. The molecular basis of this adaptation in intact circuits is not well understood. This study examines the genes active in sprouting neurons after spinal cord injury in mice. It identifies that molecules involved in lysophosphatidic acid signaling, specifically LPPR1 and LPAR1, play a role in axon growth for intact motor neurons after injury. By manipulating LPAR1 and LPPR1, either by inhibiting LPAR1 or increasing LPPR1, researchers enhanced the growth of axons and improved functional recovery in mice after brainstem lesions. This suggests these molecules are potential targets for therapies to boost axon growth and synapse formation after spinal cord injury.

Study Duration

4 weeks

Participants

Adult C57Bl6J mice

Evidence Level

Not specified

Key Findings

1
LPPR1 and LPAR1 were identified as intrinsic axon growth modulators for intact corticospinal motor neurons after adjacent injury.
2
In vivo LPAR1 inhibition or LPPR1 overexpression enhances sprouting of intact corticospinal tract axons.
3
Greater functional recovery after unilateral brainstem lesion in wild-type mice was observed after LPAR1 inhibition or LPPR1 overexpression.

Research Summary

The study identifies LPPR1 and LPAR1 as intrinsic axon growth modulators for intact corticospinal motor neurons after spinal cord injury. In vivo inhibition of LPAR1 or overexpression of LPPR1 enhances the sprouting of intact corticospinal tract axons. Modulation of the LPA-LPPR1 axis promotes functional plasticity and recovery after SCI.

Practical Implications

Therapeutic Target Identification

The identification of LPPR1 and LPAR1 provides potential therapeutic targets for enhancing axon growth and functional recovery after SCI.

Drug Development

The study suggests that pharmacological interventions targeting the LPA-LPAR1 signaling axis could promote plasticity and improve outcomes after SCI.

Spinal Circuit Plasticity

The findings support a focus on dissecting the molecular mechanisms driving plasticity-mediated functional recovery after injury.

Study Limitations

1
The study primarily uses a mouse model, and the results may not directly translate to humans.
2
The study focuses on a specific type of spinal cord injury (pyramidotomy), and the findings may not be generalizable to other types of SCI.
3
Further research is needed to fully understand the mechanisms by which LPPR1 and LPAR1 regulate axon growth and functional recovery.

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