Adenoviral gene transfer of GDNF, BDNF and TGF beta 2, but not CNTF, cardiotrophin-1 or IGF1, protects injured adult motoneurons after facial nerve avulsion.
We examined neuroprotective effects of recombinant adenoviral vectors encoding glial cell line-derived neurotrophic factor (GDNF), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT1), insulin-like growth factor-1 (IGF1), and transforming growth factor-beta2 (TGFbeta2) on lesioned adult rat facial motoneurons. The right facial nerves of adult Fischer 344 male rats were avulsed and removed from the stylomastoid foramen, and adenoviral vectors were injected into the facial canal. Animals avulsed and treated with adenovirus encoding GDNF, BDNF, CNTF, CT1, IGF1 and TGFbeta2 showed intense immunolabeling for these factors in lesioned facial motoneurons, respectively, indicating adenoviral induction of the neurotrophic factors in these neurons. The treatment with adenovirus encoding GDNF, BDNF, or TGFbeta2 after avulsion significantly prevented the loss of lesioned facial motoneurons, improved choline acetyltransferase immunoreactivity and prevented the induction of nitric oxide synthase activity in these neurons. The treatment with adenovirus encoding CNTF, CT1 or IGF1, however, failed to protect these neurons after avulsion. These results indicate that the gene transfer of GDNF and BDNF and TGFbeta2 but not CNTF, CT1 or IGF1 may prevent the degeneration of motoneurons in adult humans with motoneuron injury and motor neuron diseases.
Sakamoto
Tsuyoshi
T
Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan.
Kawazoe
Yoko
Y
Shen
Jin-Song
JS
Takeda
Yasuo
Y
Arakawa
Yoshihiro
Y
Ogawa
Junko
J
Oyanagi
Kiyomitsu
K
Ohashi
Toya
T
Watanabe
Kazutada
K
Inoue
Kiyoharu
K
Eto
Yoshikatsu
Y
Watabe
Kazuhiko
K
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis / Q000235:genetics* / Q000627:therapeutic use; D019556:COS Cells; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D020934:Ciliary Neurotrophic Factor / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use; D004622:Embryo, Mammalian; D020220:Facial Nerve Injuries / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D009046:Motor Neurons / Q000737:chemistry / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000032:analysis / Q000235:genetics* / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics* / Q000627:therapeutic use; D053781:Transforming Growth Factor beta2
D019208:Brain-Derived Neurotrophic Factor; D020934:Ciliary Neurotrophic Factor; D016207:Cytokines; C495039:GDNF protein, human; C495040:Gdnf protein, mouse; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; C509041:TGFB2 protein, human; D016212:Transforming Growth Factor beta; D053781:Transforming Growth Factor beta2; D007334:Insulin-Like Growth Factor I; C092073:cardiotrophin 1