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Reversing Persistent PTEN Activation after Traumatic Brain Injury Fuels Long-Term Axonal Regeneration via Akt/mTORC1
Ziyu Shi1, Leilei Mao1, Shuning Chen1
1State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, and Institutes of Brain Science, Fudan University, Shanghai, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|December 16, 2024
Summary
Neuronal knockout of PTEN enhances recovery after traumatic brain injury (TBI). This study reveals PTEN
Area of Science:
- Neuroscience
- Traumatic Brain Injury Research
- Molecular Biology
Background:
- Traumatic brain injury (TBI) causes lasting axonal damage and neurological deficits.
- The role of PTEN in neuronal growth is known, but its long-term changes and effects on sensory-motor circuits post-TBI are unclear.
Purpose of the Study:
- To investigate the long-term effects of neuronal PTEN knockout (PTEN-nKO) on structural and functional recovery after TBI.
- To elucidate the molecular mechanisms underlying TBI recovery involving the PTEN/Akt/mTORC1 pathway.
Main Methods:
- Neuronal knockout of PTEN (PTEN-nKO) in a TBI model.
- Diffusion tensor MRI (DTI-MRI) for white matter integrity.
- In vivo calcium imaging and electromyography for neural pathway function.
- PTEN/Raptor double knockout (PTEN/Raptor D-nKO) to assess mTORC1 mediation.
Main Results:
- PTEN-nKO significantly improved long-term structural and functional recovery post-TBI.
- DTI-MRI showed PTEN-nKO promoted white matter repair.
- Calcium imaging and EMG demonstrated PTEN-nKO facilitated cortical remapping and restored sensory-motor pathways.
- The benefits of PTEN-nKO were reversed by PTEN/Raptor D-nKO, indicating mTORC1's key role.
Conclusions:
- Persistent alterations in the PTEN/Akt/mTORC1 axis are crucial for neural circuit remodeling and cortical remapping after TBI.
- Targeting the PTEN/Akt/mTORC1 pathway offers potential therapeutic strategies for TBI recovery.
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