The effects of FGF-2 gene therapy combined with voluntary exercise on axonal regeneration across peripheral nerve gaps.
Studies were conducted to determine the possibility that voluntary exercise could enhance regenerative effects of gene therapy via Schwann cells (SC) over-expressing FGF-2. Sedentary or exercise rehabilitation conditions were therefore provided shortly after reconstructing 10mm sciatic nerve gaps in rats with silicone grafts. Exercise for 7 days elevated mRNA levels of regeneration associated proteins (GAP-43 and synapsin I) in lumbar spinal cord and dorsal root ganglia of SC transplanted, in contrast to non-cellular reconstructed rats. FGF-2 gene therapy followed by 25-27 days of exercise did enhance regeneration of myelinated axons in comparison to sedentary animals. Four weeks after surgery mRNA levels of regeneration associated proteins were significantly higher in lumbar spinal cord of running compared to sedentary SC transplanted animals. Our results suggest that voluntary exercise could reinforce the beneficial effects of SC transplantation and FGF-2 gene therapy in peripheral nerve reconstruction approaches.
Haastert
Kirsten
K
Hannover Medical School, Institute of Neuroanatomy and Center for Systems Neuroscience Hannover, Carl-Neubergstr. 1, D-30625 Hannover, Germany. Haastert.Kirsten@mh-hannover.de
Ying
Zhe
Z
Grothe
Claudia
C
Gómez-Pinilla
Fernando
F
D000818:Animals; D001369:Axons / Q000473:pathology / Q000648:ultrastructure; D017690:Cell Transplantation / Q000379:methods; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009043:Motor Activity / Q000502:physiology; D009416:Nerve Regeneration; D010805:Physical Conditioning, Animal / Q000379:methods*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016704:Synapsins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D019922:GAP-43 Protein; D012333:RNA, Messenger; D016704:Synapsins; D016222:Fibroblast Growth Factor 2