Caspase-mediated apoptosis in the cochleae contributes to the early onset of hearing loss in A/J mice

ASN Neuro
Xu HanFengchan Han

Abstract

A/J and C57BL/6 J (B6) mice share a mutation in Cdh23 (ahl allele) and are characterized by age-related hearing loss. However, hearing loss occurs much earlier in A/J mice at about four weeks of age. Recent study has revealed that a mutation in citrate synthase (Cs) is one of the main contributors, but the mechanism is largely unknown. In the present study, we showed that A/J mice displayed more severe degeneration of hair cells, spiral ganglion neurons, and stria vascularis in the cochleae compared with B6 mice. Moreover, messenger RNA accumulation levels of caspase-3 and caspase-9 in the inner ears of A/J mice were significantly higher than those in B6 mice at 2 and 8 weeks of age. Immunohistochemistry localized caspase-3 expression mainly to the hair cells, spiral ganglion neurons, and stria vascularis in cochleae. In vitro transfection with Cs short hairpin RNA (shRNA) alone or cotransfection with Cs shRNA and Cdh23 shRNA significantly increased the levels of caspase-3 in an inner ear cell line (HEI-OC1). Finally, a pan-caspase inhibitor Z-VAD-FMK could preserve the hearing of A/J mice by lowering about 15 decibels of the sound pressure level for the auditory-evoked brainstem response thresholds. In conclusion, our results ...Continue Reading

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Citations

Aug 30, 2018·Physiological Reviews·Jing Wang, Jean-Luc Puel
Apr 14, 2020·Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology·Shanshan HuangFengchan Han
Jan 18, 2020·Journal of Clinical Medicine·Jing Wang, Jean-Luc Puel
Apr 5, 2019·Journal of Nutrition and Metabolism·Yosra AlhindiAivaras Ratkevicius
Apr 8, 2019·European Archives of Oto-rhino-laryngology : Official Journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : Affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery·Seyit Mehmet CeylanMustafa Emre Gulbagci
Jan 13, 2021·International Archives of Occupational and Environmental Health·Dawei SunBaoli Zhu

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Methods Mentioned

BETA
genotyping
PCR
electrophoresis
light microscopy
confocal microscopy
Transfection
florescence microscopy
protein assay

Software Mentioned

ImageJ
GOR
USB ez
IHSS Smart EP

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