Traumatic brain injury recapitulates developmental changes of axons
Hailong Song1, Chen Chen2, Brian Kelley1
1Department of Neurosurgery, Center for Brain Injury and Repair, University of Pennsylvania, Philadelphia, PA 19104, United States.
Traumatic brain injury (TBI) may reactivate developmental axon programs. Shared molecular changes in microtubule stability suggest TBI can trigger either axon degeneration or repair pathways.
Area of Science:
- Neuroscience
- Developmental Biology
- Traumatic Brain Injury Research
Background:
- Axon degeneration and survival are critical during brain development.
- Traumatic brain injury (TBI) also involves axon degeneration and potential repair.
- The possibility that TBI re-engages developmental axon programs remains unexplored.
Purpose of the Study:
- To investigate if traumatic brain injury (TBI) recapitulates developmental axon degeneration and repair pathways.
- To compare molecular changes in axons during development and after TBI.
- To identify shared mechanisms governing axon fate after injury and during development.
Main Methods:
- Examined axonal changes in young rats during development and adult rats after TBI.
- Analyzed microtubule (MT) modifications, including tubulin post-translational modifications and associated proteins (MAPs) like tau and MAP6.
- Utilized quantitative proteomics to compare signaling pathways involved in axon degeneration and repair.
Main Results:
- Shared changes in tau phosphorylation and tubulin tyrosination were observed in degenerating axons in both development and TBI, indicating MT instability.
- Increased MAP6 expression and tubulin acetylation in non-degenerating axons suggested enhanced MT stabilization for survival or repair.
- Proteomics revealed similar signaling pathways for axon degeneration and growth/repair in both conditions.
Conclusions:
- Traumatic brain injury (TBI) may reawaken dormant developmental axon programs.
- Microtubule dynamics, regulated by proteins like tau and MAP6, play a dual role in TBI-induced axon degeneration and repair.
- Studying developmental axon biology offers insights into therapeutic strategies for TBI recovery.
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