Adenovirus-mediated NT3 gene transfer protects spiral ganglion neurons from degeneration after noise trauma / 生理学报

ABSTRACT

Numerous studies have shown that the health of spiral ganglion neurons is highly important for hearing. As a trophic factor of spiral ganglion neurons, neurotrophin 3 (NT3) is a potential candidate for prevention of spiral ganglion neuron degeneration in human. In our experiments, efficient transduction and long term expression of foreign gene of cochlea cells has been found with adenovirus carried lacZ gene (Ad-lacZ). A model of guinea pig deafness was made by intense noise exposure, which destroyed the entire organ of Corti in the middle part of the cochlea. Seven days after noise exposure, the animals were anesthetized and 1 10(8) recombinant adenoviral particles were injected into the scala tympani through the round window membrane. Animals inoculated with neurotrophin 3 adenovirus(Ad-NT3) were designated as the experimental group, animals inoculated with Ad-lacZ vector served as the control group. Four weeks after the inoculation of the virus, NT3 immunoreactivity was observed in the Ad-NT3 inoculated group. HE histochemical staining results showed that in the Ad-lacZ injected group, the neuronal degeneration was severer and the density of spiral ganglion neurons was significantly lower than those in the Ad-NT3 injected group. Our results demonstrate that with adenovirus-mediated overexpression NT3 may be developed into a new treatment to prevent secondary spiral ganglion degeneration following the damage to Corti organ.