Electrical stimulation promotes peripheral axon regeneration by enhanced neuronal neurotrophin signaling.
Electrical stimulation of cut peripheral nerves at the time of their surgical repair results in an enhancement of axon regeneration. Regeneration of axons through nerve allografts was used to evaluate whether this effect is due to an augmentation of cell autonomous neurotrophin signaling in the axons or signaling from neurotrophins produced in the surrounding environment. In the thy-1-YFP-H mouse, a single 1 h application of electrical stimulation at the time of surgical repair of the cut common fibular nerve results in a significant increase in the proportion of YFP+ dorsal root ganglion neurons, which were immunoreactive for BDNF or trkB, as well as an increase in the length of regenerating axons through allografts from wild type litter mates, both 1 and 2 weeks later. Axon growth through allografts from neurotrophin-4/5 knockout mice or grafts made acellular by repeated cycles of freezing and thawing is normally very poor, but electrical stimulation results in a growth of axons through these grafts, which is similar to that observed through grafts from wild type mice after electrical stimulation. When cut nerves in NT-4/5 knockout mice were electrically stimulated, no enhancement of axon regeneration was found. Electrical stimulation thus produces a potent enhancement of the regeneration of axons in cut peripheral nerves, which is independent of neurotrophin production by cells in their surrounding environment but is dependent on stimulation of trkB and its ligands in the regenerating axons themselves.
English
Arthur W
AW
Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA. art@cellbio.emory.edu
Schwartz
Gail
G
Meador
William
W
Sabatier
Manning J
MJ
Mulligan
Amanda
A
D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000528:radiation effects*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D004558:Electric Stimulation / Q000379:methods*; D005727:Ganglia, Spinal / Q000473:pathology; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009414:Nerve Growth Factors / Q000378:metabolism*; D009416:Nerve Regeneration / Q000528:radiation effects*; D009474:Neurons / Q000473:pathology* / Q000528:radiation effects; D010523:Peripheral Nervous System Diseases / Q000473:pathology; D020813:Receptor, trkB / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects*; D018800:Thy-1 Antigens / Q000235:genetics; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D008164:Luminescent Proteins; D009414:Nerve Growth Factors; D018800:Thy-1 Antigens; D020813:Receptor, trkB