D-dopachrome tautomerase activates COX2/PGE2 pathway of astrocytes to mediate inflammation following spinal cord injury

Journal of Neuroinflammation, 2021 · DOI: https://doi.org/10.1186/s12974-021-02186-z · Published: January 1, 2021

Simple Explanation

Astrocytes, a type of brain cell, release substances that can cause inflammation after spinal cord injury. The study found that a protein called D-DT, similar to another protein called MIF, is produced by brain cells after spinal cord injury. D-DT activates a specific inflammatory pathway (COX2/PGE2) in astrocytes through the CD74 receptor. This activation involves other intracellular proteins called MAPKs. Blocking D-DT with a specific inhibitor reduced the production of PGE2 by astrocytes, leading to improved motor function after spinal cord injury. This suggests that D-DT is a potential target for anti-inflammatory drugs to treat CNS injuries.

Study Duration

Not specified

Participants

Adult male Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
D-DT expression is induced in astrocytes and neurons, but not microglia, following spinal cord contusion, indicating a cell-specific response to injury.
2
D-DT activates the COX2/PGE2 pathway in astrocytes via the CD74 receptor, with MAPKs playing a crucial role in regulating this activation.
3
Inhibiting D-DT reduces PGE2 production by astrocytes and improves locomotor function, suggesting D-DT's role in inflammatory neuropathology.

Research Summary

This study identifies D-DT as a novel inflammatory activator of astrocytes following spinal cord injury, suggesting it could be a beneficial target for anti-inflammation drug development in neuropathological CNS conditions. The research demonstrates that D-DT, a homolog of MIF, is inducibly expressed in astrocytes and neurons after SCI, activating the COX2/PGE2 pathway via CD74 and MAPKs. Inhibition of D-DT reduces PGE2 production and improves motor function recovery, highlighting its potential as a therapeutic target for CNS inflammation post-SCI.

Practical Implications

Drug Development

D-DT could be a target for new anti-inflammatory drugs for spinal cord injury.

Targeted Therapies

Targeting D-DT in astrocytes could reduce inflammation and promote recovery.

Combination Therapy

Combining D-DT inhibitors with other treatments may improve outcomes after SCI.

Study Limitations

1
The study focuses on rat models, and results may not fully translate to humans.
2
The precise mechanisms of D-DT's cell-specific expression require further investigation.
3
Long-term effects of D-DT inhibition on spinal cord injury recovery are not fully explored.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury