Local Environment Induces Differential Gene Expression in Regenerating Nerves.

Area of Science:

• Neuroscience
• Regenerative Medicine
• Molecular Biology

Background:

• Neuromas complicate approximately 80% of amputations.
• Current management involves nerve translocation into bone or muscle, enabling regenerative neural interfaces for prosthetic feedback.
• Molecular differences in these nerve environments are not well understood.

Purpose of the Study:

• To investigate the molecular physiology of regenerating nerves in bone versus muscle environments.
• To identify gene expression differences and associated pathways in these settings.

Main Methods:

• New Zealand white rabbits underwent transfemoral amputation.
• Sciatic nerves were transposed into the femur (bone) or muscle.
• RNA sequencing was performed on nerve samples at 5 weeks post-surgery.

Main Results:

• Nerve in bone showed minimal variation with 13,028 differentially expressed genes (DEGs) compared to controls.
• Nerve in muscle showed significant variation with 12,811 DEGs.
• Both upregulated pathways related to lysosomes, phagosomes, antigen processing, and cell adhesion.
• Nerve in muscle showed further DEG-driven pathway upregulation, including immune cell signaling and extracellular matrix interactions.

Conclusions:

• Nerve housed in bone exhibits a more predictable molecular profile than nerve in muscle.
• The intramedullary canal (bone) may be a more reliable site for neuroma prevention and neural interfacing.