Effects of Different Doses of Diphtheria Toxin on the Cochlear Structure and AuditoryFunction in Wildtype Auditory-Mature Mice / 听力学及言语疾病杂志

ABSTRACT

Objective To investigate the effects of different doses of diphtheria toxin on cochlear structure and auditory function of adult wildtype mice.Methods The auditory-mature wild type C57BL/6J mice 4 weeks old were randomly devided into 50 ng/g group, 100 ng/g group and control group.C57BL/6J mice in the 50 ng/g or 100 ng/g group were injected 50 ng/g or 100 ng/g diphtheria toxin intraperitoneally for one time, respectively, and the control mice were injected equal volume of normal saline for one time.Then we investigated the ABR threshold change and morphological change of inner and outer hair cell and spiral ganglion neuron 7 days after the injection.Results At 7 day post diphtheria toxin injection compared with those of in control group, in the 50 ng/g group, there was no threshold elevation across frequencies(8 kHz ABR threshold was 20.0±3.78 and 20.83±2.04 dB SPL for 50 ng/g and control respectively), and no loss of inner and outer hair cells (for both groups, the HC loss rates were 0.3%~1%) or SGN (the SGN density was 39.45±3.65, 41.03±3.73/105 μm2, in 50 ng/g and control, respectively).However, the 100 ng/g group, compared with those of in control group, the ABR threshold (8 kHz ABR threshold was 63.0±4.47 dB SPL, respectively)was significantly elevated across each frequency(t=19.62,P<0.001), and there was significant loss of outer hair cell (the loss rate of IHC and OHC was 0.5%±0.1%, 10.7%±0.3%, respectively), which was 10% loss in the apical, middle and basal turn(t=42.219,P<0.001).And the loss of spiral ganglion neuron (the SGN density was 25.55±3.66/105 μm2) was 38%, which was significantly different from the control(t=10.985,P<0.001).Conclusion High dose injection of diphtheria toxin can cause loss of outer hair cell and spiral ganglion neuron in wild type auditory-mature C57BL/6J mice.