RhoA activation in axotomy-induced neuronal death

Exp Neurol, 2018 · DOI: 10.1016/j.expneurol.2018.04.015 · Published: August 1, 2018

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

After a spinal cord injury, severed axons in mammals often fail to regenerate due to inhibitory factors and a loss of intrinsic growth capacity. This study investigates the role of RhoA, a protein involved in inhibiting axon regeneration, in retrograde neuronal death after axotomy (axon severing). The findings suggest that RhoA activation triggers retrograde neuronal death after SCI and may be a point of convergence for inhibiting both axon regeneration and neuronal survival.

Study Duration

10 Weeks

Participants

118 Larval sea lampreys

Evidence Level

Not specified

Key Findings

1
RhoA mRNA is widely expressed in normal lamprey brain, with only slightly higher expression in poorly-regenerating neurons compared to good regenerators.
2
After spinal cord transection, RhoA mRNA accumulates in severed axon tips and is upregulated selectively in pre-apoptotic neuronal perikarya.
3
RhoA is continuously active selectively in FLICA-positive neurons (neurons undergoing apoptosis) through 9 weeks post-SCI, suggesting a role for RhoA activation in triggering retrograde neuronal death.

Research Summary

This study investigates the role of RhoA in retrograde neuronal death after spinal cord injury (SCI) in lampreys. The findings indicate that RhoA activation, rather than its mRNA expression, correlates more strongly with poor regeneration and apoptotic signaling after SCI. The results suggest that RhoA activation contributes to a neuron-intrinsic property of poor survival and poor regeneration after SCI.

Practical Implications

Therapeutic Target

RhoA may be a potential therapeutic target for promoting neuronal survival and axon regeneration after spinal cord injury.

Convergence of Signaling Pathways

RhoA may represent a convergence point for signaling pathways involved in both the inhibition of axon regeneration and the promotion of neuronal death.

CSPG-Mediated Inhibition

CSPGs may induce apoptosis and inhibit axon regeneration via RhoA activation. The CSPG pathway contributes to axotomy-induced reticulospinal neuronal death via activation of RhoA.

Study Limitations

1
The study is conducted on lampreys, and the findings may not be directly transferable to mammals.
2
The precise mechanisms by which CSPGs activate RhoA are not fully elucidated.
3
Further research is needed to determine the specific role of local translation of RhoA in injured axon tips.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury