[The transduction of neurotrophin-3/GDNF attenuates the SGNC damage in deaf mice].
OBJECTIVE
To investigate the attenuation of cisplatin-induced toxicity in the spiral ganglion neuron (SGNC) by the localized expression of the neurotrophin-3 (NT-3) and glial cell line-derived nerutrophic factor (GDNF) via HSV-Amplicon.


METHODS
We constructed the HSV-Amplicon vectors, which could express the NT-3 and GDNF under separate transcriptional control. Helper virus-free amplicon stocks were assessed in vitro for their capacity in the cultured inner ear cells. The ELISA was used to detect the production of NT-3 and GDNF. Three groups of mice were injected with cisplatin (8 mg/kg), followed by instillation of HSVnt-3myc/gdnf, HSVnt-3myc/lac or HSVlac. The numbers of SGNC were analyzed 4 weeks later.


RESULTS
The HSVnt-3myc/gdnf transduction resulted in production of NT-3 up to 11.44 micro g/ml and GDNF up to 1.79 ng/ml in cultured medium over 48 h. There were significant differences among three groups (P < 0.01). Cochleae transduced with HSVnt-3myc/gdnf and HSVnt-3myc/lac harbored from the mice had greater number of surviving SGNC. The ratio of SGNC survival (%) in HSVnt-3myc/gdnf, HSVnt-3myc/lac and HSVlac was 88%, 77% and 22%, respectively.


CONCLUSIONS
The transduction of NT-3/GDNF by HSV-Amplicon greatly attenuated SGNC the cisplatin-induced ototoxicity in mice.
Chen
Xiao-Wei
XW
Peking Union Medical College Hospital, Beijing 100730, China.
Li
Hong
H
Cao
Ke-Li
KL
Wei
Chao-Gang
CG
Jin
Xin
X
D000818:Animals; D002945:Cisplatin; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor; D034381:Hearing Loss / Q000139:chemically induced / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D020933:Neurotrophin 3 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D013136:Spiral Ganglion / Q000187:drug effects* / Q000473:pathology; D014161:Transduction, Genetic
C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D020933:Neurotrophin 3; D002945:Cisplatin