Retrograde Activation of the Extrinsic Apoptotic Pathway in Spinal-Projecting Neurons after a Complete Spinal Cord Injury in Lampreys

BioMed Research International, 2017 · DOI: https://doi.org/10.1155/2017/5953674 · Published: November 19, 2017

Spinal Cord Injury Genetics Regenerative Medicine & Stem Cells

Simple Explanation

Spinal cord injury (SCI) in mammals often leads to permanent disability because damaged nerve fibers fail to regrow. Preventing the degeneration of these nerve cells is crucial for promoting regeneration. Lampreys, unlike mammals, can recover from SCI due to their ability to regenerate nerve fibers. This study investigates the process of programmed cell death (apoptosis) in lamprey neurons after SCI. The research indicates that after SCI in lampreys, specific nerve cells degenerate slowly, and a particular apoptotic pathway (extrinsic) is involved. This pathway's activation signal travels from the injury site to the cell body via microtubules.

Study Duration

2 weeks to 4 months

Participants

57 larval sea lampreys

Evidence Level

Not specified

Key Findings

1
A significant correlation was found between the level of activated caspases (cell death markers) in identifiable neurons and their known regenerative ability after spinal cord injury in lampreys.
2
The extrinsic apoptotic pathway, specifically caspase-8, is activated in spinal cord-projecting neurons after injury, while the intrinsic pathway, involving cytochrome c release, is not.
3
Treatment with Taxol, a microtubule stabilizer, prevents the retrograde activation of caspase-8 in spinal-projecting neurons, suggesting that the death signal is transported via microtubules.

Research Summary

This study investigates the apoptotic process in lamprey descending neurons after spinal cord injury (SCI), focusing on caspase activation and the involvement of the intrinsic apoptotic pathway. The results indicate that bad-regenerating spinal cord-projecting neurons slowly degenerate after SCI, and the extrinsic pathway of apoptosis, specifically caspase-8, is involved in this process. Experiments with Taxol suggest that caspase-8 signaling is retrogradely transported by microtubules from the injury site to the neuronal soma, offering a potential therapeutic target for SCI in mammals.

Practical Implications

Therapeutic Target Identification

Preventing the retrograde activation of caspase-8 could be a therapeutic approach after SCI.

Drug Repurposing

Microtubule stabilizers like Taxol or epothilone B may prevent retrograde degeneration.

Model for CNS Injury

The sea lamprey model could be used to study the role of proapoptotic cytokines and dependence receptors in caspase-8 activation after SCI.

Study Limitations

1
The study is conducted on lampreys, and results may not be directly transferable to mammals.
2
The exact retrograde signals that activate caspase-8 are not fully elucidated.
3
The slow rate of neuronal degeneration in lampreys may be due to slower microtubule dynamics, which may differ in mammals.

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