Dose-dependent effects of ouabain on spiral ganglion neurons and Schwann cells in mouse cochlea

Abstract

Objective: This study aimed in fully investigating the toxicities of ouabain to mouse cochlea and the related cellular environment, and providing an optimal animal model system for cell transplantation in the treatment of auditory neuropathy (AN) and sensorineural hearing loss (SNHL).

Methods: Different dosages of ouabain were applied to mouse round window. The auditory brainstem responses and distortion product otoacoustic emissions were used to evaluate the cochlear function. The immunohistochemical staining and cochlea surface preparation were performed to detect the spiral ganglion neurons (SGNs), Schwann cells and hair cells.

Results: Ouabain at the dosages of 0.5 mM, 1 mM and 3 mM selectively and permanently destroyed SGNs and their functions, while leaving the hair cells relatively intact. Ouabain at 3 mM resulted in the most severe SGNs loss and induced significant loss of Schwann cells started as early as 7 days and with further damages at 14 and 30 days after ouabain exposure.

Conclusions: The application of ouabain to mouse round window induces damages of SGNs and Schwann cells in a dose- and time-dependent manner, this study established a reliable and accurate animal model system of AN and SNHL.

Chinese abstract

目的: 本研究旨在充分研究哇巴因对小鼠耳蜗和相关细胞环境的毒性, 为在治疗听神经疾病 (AN) 和感觉神经性听力损失 (SNHL) 过程中的细胞移植, 提供最佳的动物模型系统。

方法: 将不同剂量的哇巴因施于小鼠圆窗。 听觉脑干反应和畸变产物耳声发射用于评估耳蜗功能。 进行免疫史化学染色和耳蜗表面制备, 以检测螺旋神经节神经元 (SGN) 、雪旺氏细胞和毛细胞。

结果: 以0.5mM、1mM和3mM的剂量的哇巴因选择性和永久地破坏SGN及其功能, 同时使毛细胞相对完整。 3mM的哇巴因导致最严重的SGNs损失, 并诱发雪旺细胞明显损失的始发提早了7天, 并在接触哇巴因之后的14天和30天进一步损伤。

结论: 对小鼠圆窗施以哇巴因, 根据剂量和时间的不同而诱导SGN和雪旺氏细胞的损伤。本研究建立了可靠准确的AN和SNHL的动物模型系统。

Keywords:

• Ouabain
• spiral ganglion neurons
• Schwann cells
• sensorineural hearing loss
• animal model
• mouse

Acknowledgements

This work was supported by the National Natural Science Foundation of China and the Foundation of the Ministry of Education of China for Returned Scholars.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China and the Foundation of the Ministry of Education of China for Returned Scholars.