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[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.


CONCLUSION
The transduction of NT-3/GDNF by HSV-Amplicon greatly attenuated SGNC the cisplatin-induced ototoxicity in mice.