Objective To investigate the early change of cochlear ribbon synapses on inner hair cells in response to aminoglycoside ototoxicity. Methods C57BL/6J mice received intraperitoneal injection of gentamicin(100mg/kg/day), and the apical coil organ of Corti was examined on the 4th, 7th and 10 th day(n=10). Littermates without gentamicin treatment served as controls(n=10). RIBEYE on the presynaptic membrane and AMPA receptors on the postsynaptic membrane were labeled with CtBP2 or GluR2/3 respectively. Three dimension reconstruction was conducted using the 3DS MAX 8.0 software. Results There were no disruptions of outer or inner hair cells in all groups. However, the number of ribbon synapses on cochlear inner hair cells increased significantly within 7 days after gentamicin exposure(P<0.01), followed by a significant decrease after 7 days.Conclusion During the early stage of aminoglycoside ototoxicity, increased population of cochlear ribbon synapses may indicate a significant down-regulation of synaptic function.
LIU KeZHAO NingSHI ChuangWU NanLIU HuizhanZHANG YueYANG WeiyanYANG Shiming
The development of auditory synapses is a key process for the maturation of hearing function. However, it is still on debate regarding whether the development of auditory synapses is dominated by acquired sound stimulations. In this review, we summarize relevant publications in recent decades to address this issue. Most reported data suggest that extrinsic sound stimulations do affect, but not govern the development of periphery auditory synapses. Overall, periphery auditory synapses develop and mature according to its intrinsic mechanism to build up the synaptic connections between sensory neurons and/or interneurons.
Objective To study characteristics of hearing loss after exposure to moderate noise exposure in C57BL/6J mice.Methods Male C57BL/6J mice with normal hearing at age of 5-6 weeks were chosen for this study.The mice were randomly selected to be studied immediately after exposure(Group P0),or 1 day(Group P1),3 days(Group P3),7 days(Group P7)or 14 days(P14)after exposure.Their before exposure condition served as the normal control.All mice were exposed to a broad-band white noise at 100 dB SPL for 2 hours,ABR thresholds were used to estimate hearing status at each time point.Results ABR threshold elevation was seen at every tested frequency at P0(P<0.01).Elevation at high-frequencies(16 kHz and 32 kHz)was greater than at lower frequencies(4 kHz and 8 kHz,P<0.05).From P1 to P14,ABR thresholds continuously improved,and there was no significant difference between P14 and before exposure(P>0.05).Conclusion There is a frequency specific response to 100 dB SPL broad-band white noise in C57BL/6J mice,with the high-frequency being more susceptible.Hearing loss induced by moderate noise exposure appears reversible in C57BL/6J mice.
Objective To study presynaptic alternations of cochlear ribbons arising from aminoglycoside ototoxic stimuli in C57BL/6J mice. Methods Animals were injected with low dose gentamicin(100 mg/kg/day) for14 days, From the 14 th to 28 th days, the mice were maintained free of gentamicin treatment. Immunohistochemistry labeling was employed to trace RIBEYE, a major presynaptic componment of ribbon synapses.RIBEYE/CtBP2 expression levels were assessed and compared with hearing threshold shifts. Auditory function was assessed by auditory brainstem responses. The stereocilia of outer hair cells(OHCs) and IHCs was examined by scanning electron microscopy(SEM). Results Hearing thresholds were elevated with peak hearing loss observed on the 7th day after gentamicin exposure, followed by improvement after the 7th day.RIBEYE/CtBP2 expression directly correlated with observed hearing threshold shifts. Strikingly, we did not see any obvious changes in stereocilia in both OHCs and IHCs until the 28 th day. Mild changes in stereocilia were only observed in OHCs on the 28 th day. Conclusions These findings indicate that presynapse cochlear ribbons, rather than stereocilia, may be sensitive to aminoglycoside ototoxic exposure in mice cochleae. A pattern of RIBEYE/CtBP2 expression changes seems to parallel hearing threshold shifts and suggests presynaptic response properties to lower dosage of aminoglycoside ototoxic stimuli.
LIU KeWANG XiaoyuLI SijunTANG SiquanXU YiceWANG XuefengSUN JianheYANG WeiyanYANG Shiming
