ERK1/2-Mediated Schwann Cell Proliferation in the Regenerating Sciatic Nerve by Treadmill Training

Male 0301 basic medicine 0303 health sciences Mitogen-Activated Protein Kinase 3 Proto-Oncogene Proteins c-jun Growth Cones Denervation Exercise Therapy Nerve Regeneration Rats Enzyme Activation Rats, Sprague-Dawley Disease Models, Animal 03 medical and health sciences GAP-43 Protein Ganglia, Spinal Physical Conditioning, Animal Exercise Test Neurites Animals RNA, Messenger Enzyme Inhibitors Cell Proliferation
DOI: 10.1089/neu.2008.0711 Publication Date: 2009-10-15T18:33:31Z
ABSTRACT
Proliferation of Schwann cells in the injured peripheral nerve supports axonal regeneration, and physical training in experimental animals has been shown to promote nerve regeneration. Extracellular signal-regulated kinase 1/2 (ERK1/2) activity can mediate neuronal responses to lesion signals, but its role in non-neuronal cells in the injured area is largely unknown. Here we report that treadmill training (TMT) facilitates axonal regeneration via the upregulation of phospho-ERK1/2 protein levels in Schwann cells in the injured sciatic nerve. Low-intensity, but not high-intensity, TMT increased neurite outgrowth of dorsal root ganglion (DRG) sensory neurons and potentiated Schwann cell proliferation. TMT elevated levels of GAP-43 mRNA and protein, and phospho-ERK1/2 protein in the injured sciatic nerves. TMT also enhanced phospho-c-Jun protein levels in the injured nerve. In-vivo administration of the ERK1/2 inhibitor PD98059 eliminated phospho-c-Jun, suggesting ERK1/2 phosphorylation of the c-Jun protein. PD98059 treatment decreased levels of BrdU-labeled proliferating Schwann cells in the distal portion of the injured nerve, and delayed the axonal regrowth that was promoted by TMT. The present data suggest that increased ERK1/2 activity in Schwann cells may play an important role in TMT-mediated enhancement of axonal regeneration in the injured peripheral nerve.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (41)
CITATIONS (47)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....