Integration of engrafted Schwann cells into injured peripheral nerve: axonal association and nodal formation on regenerated axons.
Transplantation of myelin-forming cells can remyelinate axons, but little is known of the sodium channel organization of axons myelinated by donor cells. Sciatic nerve axons of female wild type mice were transected by a crush injury and Schwann cells (SCs) from green fluorescence protein (GFP)-expressing male mice were transplanted adjacent to the crush site. The male donor cells were identified by GFP fluorescence and fluorescence in situ hybridization (FISH) for Y chromosome. In nerves of GFP-expressing mice, GFP was observed in the axoplasm and in the cytoplasmic compartments of the Schwann cells, but not in the myelin. Following transplantation of GFP-SCs into crushed nerve of wild type mice, immuno-electron microscopic analysis indicated that GFP was observed in the cytoplasmic compartments of engrafted Schwann cells which formed myelin. Nodal and paranodal regions of the axons myelinated by the GFP-SCs were identified by Na(v)1.6 sodium channel and Caspr immunostaining, respectively. Nuclear identification of the Y chromosome by FISH confirmed the donor origin of the myelin-forming cells. These results indicate that engrafted GFP-SCs participate in myelination of regenerated peripheral nerve fibers and that Na(v)1.6 sodium channel, which is the dominant sodium channel at normal nodes, is reconstituted on the regenerated axons.
Radtke
Christine
C
Department of Neurology, LCI 7, P.O. Box 208018, Yale University School of Medicine, New Haven, CT 06516, USA.
Akiyama
Yukinori
Y
Lankford
Karen L
KL
Vogt
Peter M
PM
Krause
Diane S
DS
Kocsis
Jeffery D
JD
D000818:Animals; D019771:Axotomy; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002451:Cell Compartmentation / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism / Q000648:ultrastructure; D004195:Disease Models, Animal; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D009186:Myelin Sheath / Q000502:physiology* / Q000648:ultrastructure; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D059348:Peripheral Nerve Injuries; D010525:Peripheral Nerves / Q000601:surgery / Q000648:ultrastructure; D011901:Ranvier's Nodes / Q000502:physiology* / Q000648:ultrastructure; D012583:Schwann Cells / Q000502:physiology / Q000637:transplantation* / Q000648:ultrastructure; D020426:Sciatic Neuropathy / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D015222:Sodium Channels / Q000378:metabolism; D014998:Y Chromosome / Q000235:genetics / Q000378:metabolism
D015816:Cell Adhesion Molecules, Neuronal; C491322:Cntnap1 protein, mouse; D062557:NAV1.6 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C491046:Scn8a protein, mouse; D015222:Sodium Channels; D049452:Green Fluorescent Proteins