ERK1/2-mediated Schwann cell proliferation in the regenerating sciatic nerve by treadmill training.
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.
Seo
Tae Beom
TB
Department of Oriental Medicine, Daejeon University, Daejeon, Korea.
Oh
Myung-Jin
MJ
You
Byoung-Gun
BG
Kwon
Ku-Birm
KB
Chang
In-Ae
IA
Yoon
Jin-Hwan
JH
Lee
Chan-Yong
CY
Namgung
Uk
U
D000818:Animals; D049109:Cell Proliferation; D003714:Denervation; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005080:Exercise Test; D005081:Exercise Therapy / Q000379:methods*; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D010805:Physical Conditioning, Animal / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology / Q000201:enzymology*; D012584:Sciatic Nerve / Q000166:cytology / Q000293:injuries / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000201:enzymology* / Q000503:physiopathology / Q000534:rehabilitation*; D015854:Up-Regulation / Q000502:physiology
D004791:Enzyme Inhibitors; D019922:GAP-43 Protein; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D048052:Mitogen-Activated Protein Kinase 3