mTOR regulates peripheral nerve response to tensile strain

Area of Science:

• Neuroscience
• Cellular Biology
• Biochemistry

Background:

• Peripheral nerves encounter tensile strain during development and movement.
• Excessive strain is detrimental, but moderate strain can promote neuronal outgrowth.
• Mechanisms underlying nerve response to strain are not fully understood.

Purpose of the Study:

• To investigate signaling mechanisms in peripheral nerves responding to deformation.
• To explore the role of mammalian target of rapamycin (mTOR) in nerve strain response.
• To understand the impact of strain on structural protein expression and axonal protein synthesis.

Main Methods:

• In vivo rat model of sciatic nerve strain (11% deformation for 6 hours).
• Western blotting to analyze protein levels (mTOR, S6, MBP, β-actin, NF-H, tubulin).
• Systemic rapamycin treatment to inhibit mTORC1.
• Cultured dorsal root ganglion neurons with puromycin incorporation assay for protein synthesis.

Main Results:

• Nerve strain did not impair compound action potential latency or amplitude.
• Strain upregulated mTOR/S6 signaling, increased myelin basic protein (MBP), β-actin, and NF-H phosphorylation.
• Rapamycin treatment suppressed mTOR/S6 signaling, reduced MBP and tubulin, and decreased NF-H phosphorylation.
• Strain increased axonal protein synthesis in cultured neurons.

Conclusions:

• Moderate tensile strain activates mTOR signaling pathways in peripheral nerves.
• mTOR signaling is crucial for increasing MBP expression, NF-H phosphorylation, and maintaining tubulin levels under strain.
• Neuronal translational pathways respond to mechanical strain, impacting nerve development and regeneration strategies.