PMID- 16473328 OWN - NLM STAT- MEDLINE DCOM- 20060725 LR - 20121115 IS - 0006-8993 (Print) IS - 0006-8993 (Linking) VI - 1076 IP - 1 DP - 2006 Mar 3 TI - Adenoviral gene transfer of BDNF and GDNF synergistically prevent motoneuron loss in the nucleus ambiguus. PG - 1-8 AB - 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. FAU - Moro, Kazuhisa AU - Moro K AD - Department of Otolaryngology-Head and Neck Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo 1608582, Japan. FAU - Shiotani, Akihiro AU - Shiotani A FAU - Watabe, Kazuhiko AU - Watabe K FAU - Takeda, Yasuo AU - Takeda Y FAU - Saito, Koichiro AU - Saito K FAU - Mori, Yuko AU - Mori Y FAU - Ogawa, Kaoru AU - Ogawa K LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060213 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (RNA, Messenger) RN - EC 1.6.99.1 (NADPH Dehydrogenase) SB - IM MH - Adenoviridae/physiology MH - Animals MH - Brain-Derived Neurotrophic Factor/biosynthesis/genetics/*therapeutic use MH - Cell Count/methods MH - Disease Models, Animal MH - Functional Laterality MH - Gene Transfer Techniques MH - *Genetic Therapy MH - Glial Cell Line-Derived Neurotrophic Factor/biosynthesis/genetics/*therapeutic use MH - Immunohistochemistry/methods MH - Male MH - Motor Neurons/drug effects/*physiology MH - NADPH Dehydrogenase/metabolism MH - Nerve Degeneration/etiology/*prevention & control MH - Nucleus Accumbens/drug effects/*pathology MH - RNA, Messenger/genetics/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Reverse Transcriptase Polymerase Chain Reaction/methods MH - Time Factors MH - Vagus Nerve Diseases/complications/pathology EDAT- 2006/02/14 09:00 MHDA- 2006/07/26 09:00 CRDT- 2006/02/14 09:00 PHST- 2005/05/11 00:00 [received] PHST- 2005/11/04 00:00 [revised] PHST- 2005/12/30 00:00 [accepted] PHST- 2006/02/14 09:00 [pubmed] PHST- 2006/07/26 09:00 [medline] PHST- 2006/02/14 09:00 [entrez] AID - S0006-8993(06)00008-4 [pii] AID - 10.1016/j.brainres.2005.12.119 [doi] PST - ppublish SO - Brain Res. 2006 Mar 3;1076(1):1-8. doi: 10.1016/j.brainres.2005.12.119. Epub 2006 Feb 13.