The Rheb–mTOR Pathway Is Upregulated in Reactive Astrocytes of the Injured Spinal Cord

The Journal of Neuroscience, 2009 · DOI: 10.1523/JNEUROSCI.4103-08.2009 · Published: January 28, 2009

Simple Explanation

Astrocytes, a type of cell in the central nervous system, react to tissue damage by becoming reactive, which involves migration, hypertrophy, and formation of a glial scar. This glial scar inhibits axon regeneration, making it a target for therapeutic strategies to improve functional recovery after spinal cord injury. The study found that the Rheb-mTOR pathway, a key regulator of cell growth and proliferation, is activated in these reactive astrocytes, suggesting it plays a role in their response to spinal cord injury.

Study Duration

Not specified

Participants

Adult male Sprague Dawley rats

Evidence Level

Not specified

Key Findings

1
EGF activates the mTOR pathway in cultured adult spinal cord astrocytes through Akt-mediated phosphorylation of Tuberin, leading to Rheb activation.
2
Rheb is essential for EGF-dependent mTOR activation in spinal cord astrocytes, while the Ras-MAP kinase pathway is not involved.
3
The mTOR-selective drug rapamycin inhibits astrocyte growth, EGF-dependent chemoattraction, and reduces signs of reactive gliosis in injured rats.

Research Summary

This study demonstrates that the EGF receptor, when activated in astrocytes, triggers a signaling pathway involving Akt, Tuberin, Rheb, and mTOR. The research also shows that this pathway is functional in reactive astrocytes in vivo in a model of spinal cord injury, where increased levels of activated EGF receptor and Rheb were observed. Furthermore, rapamycin treatment reduced reactive gliosis in the injured spinal cord, suggesting it could be used to modulate astrocytic responses in the damaged nervous system.

Practical Implications

Therapeutic Target

The Rheb-mTOR pathway represents a potential therapeutic target for modulating astrocyte responses after spinal cord injury.

Rapamycin Application

Rapamycin, already used as an immunosuppressant, could be beneficial in treating spinal cord injury by reducing astrocyte proliferation and migration.

Combination Therapy

Rapamycin may be used in combination with EGF receptor inhibitors to reduce glial scar formation after spinal cord injury.

Study Limitations

1
The study focuses on an ischemic model of spinal cord injury, and results may not be generalizable to other types of injuries.
2
The in vivo effects of rapamycin on functional recovery after spinal cord injury require further investigation.
3
The precise mechanisms by which rapamycin affects astrocyte migration and gliosis need further elucidation.

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