Tumor necrosis factor-alpha-mutant mice exhibit high frequency hearing loss

Naoki Oishi, Jun Chen, Hong Wei Zheng, Kayla Hill, Jochen Schacht, Su Hua Sha

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Exogenous tumor necrosis factor-alpha (TNF-α) plays a role in auditory hair cell death by altering the expression of apoptosis-related genes in response to noxious stimuli. Little is known, however, about the function of TNF-α in normal hair cell physiology. We, therefore, investigated the cochlear morphology and auditory function of TNF-α-deficient mice. Auditory evoked brainstem response showed significantly higher thresholds, especially at higher frequencies, in 1-month-old TNF-α-/- mice as compared to TNF-α+/- and wild type (WT); hearing loss did not progress further from 1 to 4 months of age. There was no difference in the gross morphology of the organ of Corti, lateral wall, and spiral ganglion cells in TNF-α-/- mice compared to WT mice at 4 months of age, nor were there differences in the anatomy of the auditory ossicles. Outer hair cells were completely intact in surface preparations of the organ of Corti of TNF-α-/- mice, and synaptic ribbon counts of TNF-α-/- and WT mice at 4 months of age were similar. Reduced amplitudes of distortion product otoacoustic emissions, however, indicated dysfunction of outer hair cells in TNF-α-/- mice. Scanning electron microscopy revealed that stereocilia were sporadically absent in the basal turn and distorted in the middle turn. In summary, our results demonstrate that TNF-α-mutant mice exhibit early hearing loss, especially at higher frequencies, and that loss or malformation of the stereocilia of outer hair cells appears to be a contributing factor.

Original languageEnglish
Pages (from-to)801-811
Number of pages11
JournalJARO - Journal of the Association for Research in Otolaryngology
Volume14
Issue number6
DOIs
Publication statusPublished - 2013 Dec 1
Externally publishedYes

Keywords

  • TNF-alpha-deficient mice
  • higher frequency hearing loss
  • malformation of the stereocilia of outer hair cells

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Sensory Systems

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