The immunosuppressant FK506 increases GAP-43 mRNA levels in axotomized sensory neurons.
FK506, an immunosuppressant drug used to prevent allograft rejection in organ transplantations, accelerates functional recovery and nerve regeneration in the rat sciatic nerve crush model. While the mechanism by which FK506 increases regeneration is unknown, in contrast to immunosuppression, it does not involve calcineurin inhibition. Using the reverse-transcriptase polymerase chain reaction (RT-PCR) technique and a digoxigenin-labeled probe, we show that subcutaneous injections of FK506 (10 mg/kg/day) markedly increases the level of axotomy-induced growth-associated protein (GAP-43) mRNA in dorsal root ganglion (DRG) neurons. Quantitation of DRG neurons revealed that FK506 produced a 33% increase in the numbers of neurons exhibiting intense staining. Increased synthesis of GAP-43 may play a role in FK506's ability to speed nerve regeneration.
Gold
B G
BG
Center for Research on Occupational and Environmental Toxicology, Oregon Health Sciences University, Portland 97201, USA.
Yew
J Y
JY
Zeleny-Pooley
M
M
D000818:Animals; D019771:Axotomy; D019922:GAP-43 Protein / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000502:physiology; D016559:Tacrolimus / Q000008:administration & dosage*
D019922:GAP-43 Protein; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016559:Tacrolimus