Identification of regenerative processes in neonatal spinal cord injury in the opossum (Monodelphis domestica): A transcriptomic study

J Comp Neurol, 2021 · DOI: 10.1002/cne.24994 · Published: January 1, 2021

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study examines how the spinal cord of opossums responds to injury at different ages. Young opossums can regenerate their spinal cords after injury, while older ones cannot. The researchers used RNA sequencing to identify which genes are turned on or off after spinal cord injury in young (regenerating) and older (non-regenerating) opossums. The study found that the genetic response to spinal cord injury is more complex in non-regenerating spinal cords, suggesting that non-neuronal cells play a strong role in the outcome after injury.

Study Duration

7 days

Participants

Opossum pups at postnatal Day 7 or 28 (P7SCI and P28SCI)

Evidence Level

Not specified

Key Findings

1
The study identified 558 genes whose expression changed after spinal cord injury, with most being upregulated.
2
Gene ontology analysis revealed that immune-related functions were overrepresented in both regenerating and non-regenerating cords, but non-regenerating cords also showed overrepresentation in cell proliferation, cell adhesion, and apoptosis.
3
Cell-type association analysis suggested that injury-associated gene transcripts were most strongly associated with microglia and endothelial cells, regardless of injury age.

Research Summary

This study used RNA sequencing to examine gene expression profiles in regenerating and nonregenerating spinal cords of opossums after injury at different ages. The study demonstrated a more complex and dynamic response to injury in nonregenerating cords compared to regenerating cords. The findings provide a list of genes that respond to spinal cord injury in cords that regenerate and those that do not, offering a resource for determining genes important for spinal cord regeneration.

Practical Implications

Potential Therapeutic Targets

Identified genes could serve as potential targets for therapeutic interventions aimed at promoting spinal cord regeneration.

Understanding Immune Response

Differences in immune responses between regenerating and non-regenerating cords can inform strategies to modulate inflammation after spinal cord injury.

Cell-Specific Therapies

The strong association of gene transcripts with microglia and endothelial cells suggests that targeting these cell types may be beneficial for promoting regeneration.

Study Limitations

1
The study focused on a specific animal model (opossum), and results may not be directly transferable to humans.
2
The analysis only covered the first week after injury, limiting insights into long-term regenerative processes.
3
The study used a conservative approach for identifying differentially expressed genes, potentially missing subtle changes in gene expression.

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