Ribbon Synapses and Hearing Impairment in Mice After in utero Sevoflurane Exposure

Abstract

Introduction

In utero, exposure to sevoflurane (a commonly used inhalation anesthetic) can lead to hearing impairment in offspring mice, but the underlying impairment mechanism is not known.

Materials and Methods

Day-15 pregnant mice were treated with 2.5% sevoflurane for 2 h to investigate sevoflurane ototoxicity. Cochleae from offspring mice were harvested for hair-cell and ribbon-synapse assessments. Hearing in offspring mice was assessed at postnatal day 30 using an auditory brainstem-response (ABR) test. Cochlear-explant cultures from offspring mice were exposed to 2.5% sevoflurane for 6 h. Immediately after treatment, explants were assessed for hair-cell morphology, mitochondrial oxidative stress, and autophagy.

Results

In utero, sevoflurane exposure impaired hearing in the offspring is demonstrated by a decrease in ABR wave I amplitudes, a marker for ribbon-synapse functionality. Sevoflurane exposure caused no obvious damage to hair cells, but cochlear ribbon synapses were reduced in postnatal day 15 offspring, and partially recovered by postnatal day 30. Sevoflurane treatment also increased mitochondrial reactive-oxygen species stress and decreased autophagy in the cochlear explants.

Conclusion

These results suggest that oxidative stress and reduced autophagy may underly ribbon-synapse involvement in sevoflurane-induced hearing loss.

Keywords:

• sevoflurane
• hearing impairment
• ribbon synapse
• hair cells
• cochlea

Funding

Funding was provided by the National Natural Science Foundation of China (Grant #81671045). We acknowledge Professor Huawei Li for technical support and critical discussions.

Author Contributions

Xia Shen and Huiqian Yu designed the study. Xia Yuan, Hongjun Liu, Yufeng Li, and Wen Li conducted the study. Xia Shen and Huiqian Yu analyzed the data. Xia Yuan carried out the in vivo study. Hongjun Liu carried out the in vitro study. Xia Shen and Huiqian Yu wrote the manuscript, and all other authors participated in manuscript revisions. All Authors contributed toward data analysis, drafting and revising the paper and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.