Axonal regrowth downregulates the synthesis of glial cell line-derived neurotrophic factor in the lesioned rat sciatic nerve.
The effect of axonal regeneration on de novo synthesis of glial cell line-derived neurotrophic factor (GDNF) in rat sciatic nerves was examined. Transection of the sciatic nerve caused a prominent increase in the GDNF content in the distal segments within 1 week. The high level was sustained until 4 weeks in the animal model in which the nerve ends were ligated with thread (non-regeneration group); however, it was reduced to the original level within 2 or 4 weeks after the transection only in the segments invaded by regenerating axons in the models in which the nerve ends were coaptated (regeneration group). Expression of both GDNF protein and mRNA was decreased with a reciprocal increase in the density of neurofilaments, used as a marker of axonal ingrowth in distal segments of the regeneration group, suggesting that axonal contact turned off the GDNF-mediated nerve regeneration activity.
Yamada
Yoshihisa
Y
Laboratory of Molecular Biology, Gifu Pharmaceutical University, Mitahora-higashi, Japan.
Shimizu
Katsuji
K
Nitta
Atsumi
A
Soumiya
Hitomi
H
Fukumitsu
Hidefumi
H
Furukawa
Shoei
S
D000704:Analysis of Variance; D000818:Animals; D001369:Axons / Q000502:physiology*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism; D009414:Nerve Growth Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D020426:Sciatic Neuropathy / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors
C495039:GDNF protein, human; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D011994:Recombinant Proteins