Adenoviral gene transfer of BDNF and GDNF synergistically prevent motoneuron loss in the nucleus ambiguus

Kazuhisa Moro; Akihiro Shiotani; Kazuhiko Watabe; Yasuo Takeda; Koichiro Saito; Yuko Mori; Kaoru Ogawa

doi:10.1016/j.brainres.2005.12.119

Adenoviral gene transfer of BDNF and GDNF synergistically prevent motoneuron loss in the nucleus ambiguus

Kazuhisa Moro, Akihiro Shiotani, Kazuhiko Watabe, Yasuo Takeda, Koichiro Saito, Yuko Mori, Kaoru Ogawa

Research output: Contribution to journal › Article › peer-review

29 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	1-8
Number of pages	8
Journal	Brain Research
Volume	1076
Issue number	1
DOIs	https://doi.org/10.1016/j.brainres.2005.12.119
Publication status	Published - 2006 Mar 3
Externally published	Yes

Keywords

Avulsion
BDNF
GDNF
Laryngeal paralysis
Motoneuron
Nucleus ambiguus

ASJC Scopus subject areas

Neuroscience(all)
Molecular Biology
Clinical Neurology
Developmental Biology

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10.1016/j.brainres.2005.12.119

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title = "Adenoviral gene transfer of BDNF and GDNF synergistically prevent motoneuron loss in the nucleus ambiguus",

abstract = "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.",

keywords = "Avulsion, BDNF, GDNF, Laryngeal paralysis, Motoneuron, Nucleus ambiguus",

author = "Kazuhisa Moro and Akihiro Shiotani and Kazuhiko Watabe and Yasuo Takeda and Koichiro Saito and Yuko Mori and Kaoru Ogawa",

note = "Funding Information: We wish to thank Dr. Jing-Song Shen (Jikei University School of Medicine) for adenovirus preparation and Yoko Kawazoe (Tokyo Metropolitan Institute for Neuroscience) for tissue sectioning. This work was supported in part by a Grant-in-Aid for Encouragement of Young Scientists (B) (No. 14770922) and a Grant-in-Aid for Scientific Research (C) (No. 15591831) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by National Grant-in-Aid for the Establishment of High-Tech Research Center in a Private University. A summary of this work was presented at Research Forum at the Annual Meeting of the American Academy of Otolaryngology-Head and Neck Surgery in San Diego, CA, September, 22–25, 2002.",

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AU - Moro, Kazuhisa

AU - Shiotani, Akihiro

AU - Watabe, Kazuhiko

AU - Takeda, Yasuo

AU - Saito, Koichiro

AU - Mori, Yuko

AU - Ogawa, Kaoru

N1 - Funding Information: We wish to thank Dr. Jing-Song Shen (Jikei University School of Medicine) for adenovirus preparation and Yoko Kawazoe (Tokyo Metropolitan Institute for Neuroscience) for tissue sectioning. This work was supported in part by a Grant-in-Aid for Encouragement of Young Scientists (B) (No. 14770922) and a Grant-in-Aid for Scientific Research (C) (No. 15591831) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by National Grant-in-Aid for the Establishment of High-Tech Research Center in a Private University. A summary of this work was presented at Research Forum at the Annual Meeting of the American Academy of Otolaryngology-Head and Neck Surgery in San Diego, CA, September, 22–25, 2002.

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N2 - 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.

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.

KW - Avulsion

KW - BDNF

KW - GDNF

KW - Laryngeal paralysis

KW - Motoneuron

KW - Nucleus ambiguus

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Adenoviral gene transfer of BDNF and GDNF synergistically prevent motoneuron loss in the nucleus ambiguus

Abstract

Keywords

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