Thyroid hormones stimulate expression and modification of cytoskeletal protein during rat sciatic nerve regeneration.
Peripheral neurons can regenerate after axotomy; in this process, the role of cytoskeletal proteins is important because they contribute to formation and reorganization, growth, transport, stability and plasticity of axons. In the present study, we examined the effects of thyroid hormones (T3) on the expression of major cytoskeletal proteins during sciatic nerve regeneration. At various times after sciatic nerve transection and T3 local administration, segments of operated nerves from T3-treated rats and control rats were examined by Western blotting for the presence of neurofilament, tubulin and vimentin. Our results revealed that, during the first week after surgery, T3 treatment did not significantly alter the level of NF subunits and tubulin in the different segments of operated nerves compared to control nerves. Two or 4 weeks after operation, the concentration of NF-H and NF-M isoforms was clearly increased by T3 treatment. Moreover, under T3-treatment, NF proteins appeared more rapidly in the distal segment of operated nerves. Likewise, the levels of betaIII, and of acetylated and tyrosinated tubulin isotypes, were also up-regulated by T3-treatment during regeneration. However, only the tyrosinated tubulin form appeared earlier in the distal nerve segments. At this stage of regeneration, T3 had no effect on the level of vimentin expression. In conclusion, thyroid hormone improves and accelerates peripheral nerve regeneration and exerts a positive effect on cytoskeletal protein expression and transport involved in axonal regeneration. These results help us to understand partially the mechanism by which thyroid hormones enhance peripheral nerve regeneration. The stimulating effect of T3 on peripheral nerve regeneration may have considerable therapeutic potential.
Schenker
Michel
M
Institute of Cell Biology and Morphology (IBCM), Medical School, Lausanne, Switzerland.
Riederer
Beat Michel
BM
Kuntzer
Thierry
T
Barakat-Walter
Ibtissam
I
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D016900:Neurofilament Proteins / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D012828:Silicones / Q000627:therapeutic use; D014284:Triiodothyronine / Q000378:metabolism / Q000494:pharmacology*; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology; D014746:Vimentin / Q000187:drug effects / Q000378:metabolism
D003598:Cytoskeletal Proteins; D016900:Neurofilament Proteins; D012828:Silicones; D014404:Tubulin; D014746:Vimentin; C044882:neurofilament protein L; D014284:Triiodothyronine; C061195:neurofilament protein M