Tohoku J. Exp. Med., 2023 July, 260(3)

Effects of Ndufs4 Deletion on Hearing after Various Acoustic Exposures

Tomotaka Hemmi,¹ Jun Suzuki,¹ Yoshiteru Kagawa,² Yohei Honkura,¹ Ryoukichi Ikeda,³ Ken Hashimoto,¹ Chitose Suzuki,⁴ Tetsuaki Kawase,^1,5Takaaki Abe,⁴ Yuji Owada² and Yukio Katori¹

¹Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
²Department of Organ Anatomy, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
³Department of Otolaryngology, Head and Neck Surgery, Iwate Medical University School of Medicine, Shiwa-gun, Iwate, Japan
⁴Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
⁵Laboratory of Rehabilitative Auditory Science, Tohoku University Graduate School of Biomedical Engineering, Sendai, Miyagi, Japan

Mitochondrial dysfunction can cause cochlear dysfunction and accelerate noise-induced hearing loss (NIHL). NADH dehydrogenase (ubiquinone) Fe-S protein 4 (Ndufs4) is one of the subunits of mitochondrial complex I and has a role in the assembly and stabilization of complex I. However, the involvement of Ndufs4 in the pathogenesis of NIHL has not been reported. The aim of this study was to evaluate whether Ndufs4 deletion causes vulnerability to noise exposures. The wild-type (WT) and Ndufs4 knockout (KO) mice with C57BL/6J genetic background were used. Cochlear histology and hearing thresholds were assessed after noise exposure at 100 or 86 dB sound pressure level (SPL). Immunostaining showed the widespread expression of Ndufs4 in the cochlea. After noise exposure at 100 dB SPL, auditory brainstem response (ABR) threshold shifts at 4 kHz in Ndufs4 KO mice were significantly higher than that in WT mice. After noise exposure at 86 dB SPL, ABR threshold shifts, wave 1 amplitudes, and the number of synapses in the inner hair cells were not significantly different. RNA sequencing revealed the decreased expression of energy generation-related genes in Ndufs4 KO mice. Ndufs4 deficiency accelerates permanent low-frequency threshold shifts after moderate noise exposure.

Key words —— hair cell; mitochondrial dysfunction; Ndufs4; noise-induced hearing loss; synapse

© 2023 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2023 July, 260(3), 181-191.

Correspondence: Jun Suzuki, Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan.

e-mail: j_suzuki1212@orl.med.tohoku.ac.jp

*These two authors contributed equally to this work.