Adenoviral gene transfer of BDNF and GDNF synergistically prevent motoneuron loss in the nucleus ambiguus.
We have previously shown that neuroprotective effects of an adenoviral glial cell line-derived neurotrophic factor (GDNF) gene transfer on the lesioned adult rat motoneurons in the nucleus ambiguus. In the present study, we examined neuroprotective effects of adenoviral gene transfer of brain-derived neurotrophic factor (BDNF) or/and GDNF to motoneurons in nucleus ambiguus using an adult rat vagal nerve avulsion model. The animals avulsed and inoculated with adenoviral vectors encoding BDNF (AxCAmBDNFME) or/and GDNF (AxCAhGDNF) showed immunolabeling for BDNF or/and GDNF in the nucleus ambiguus on the treated side, respectively, and expression of virus-induced BDNF or/and GDNF mRNA transcripts in the brainstem tissue that contained the nucleus ambiguus of the treated side. The treatment with AxCAhGDNF or AxCAmBDNFME significantly prevented the loss of vagal motoneurons in comparison to the control; the protective effect of AxCAmBDNFME was greater than that of AxCAhGDNF. The combined treatment with AxCAmBDNFME and AxCAhGDNF acted synergistically and significantly larger number of vagal motoneurons was preserved as compared to either AxCAmBDNFME treatment or AxCAhGDNF treatment. The treatment with AxCAmBDNFME or/and AxCAhGDNF after avulsion also suppressed the activity of nitric oxide synthase in lesioned motoneurons in the nucleus ambiguus. These results indicate that adenovirus-mediated BDNF and GDNF gene transfer may prevent the degeneration of motoneurons in humans after either vagal nerve injury or recurrent laryngeal nerve injury.
Department of Otolaryngology-Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 1608582, Japan.
Kazuhisa
K
Moro
Akihiro
A
Shiotani
Kazuhiko
K
Watabe
Yasuo
Y
Takeda
Koichiro
K
Saito
Yuko
Y
Mori
Kaoru
K
Ogawa
D000256:Adenoviridae / Q000502:physiology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D007839:Functional Laterality; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009410:Nerve Degeneration / Q000209:etiology / Q000517:prevention & control*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors; D020421:Vagus Nerve Diseases / Q000150:complications / Q000473:pathology
D019208:Brain-Derived Neurotrophic Factor; D051100:Glial Cell Line-Derived Neurotrophic Factor; D012333:RNA, Messenger; D009252:NADPH Dehydrogenase