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Modified Experimental Conditions for Noise-Induced Hearing Loss in Mice and Assessment of Hearing Function and Outer Hair Cell Damage
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Nr4a1 Deficiency Potentially Promotes Hearing Loss Through Inner Ear Immunity in C57BL/6N Mice.

Yanbing Lai1, Xiaodi Wang1, Maohua Wang2

  • 1Department of Otorhinolaryngology Head and Neck Surgery, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei.

Otology & Neurotology : Official Publication of the American Otological Society, American Neurotology Society [And] European Academy of Otology and Neurotology
|October 16, 2025
PubMed
Summary

Nuclear receptor subfamily 4 group A member 1 (Nr4a1) deficiency worsens age-related hearing loss. This involves cochlear nerve fiber damage and altered gene expression, highlighting Nr4a1’s role in auditory health.

Keywords:
Auditory nerve fibersHearing lossInner ear immunityNr4a1Ribbons reduction

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Area of Science:

  • Otolaryngology
  • Genetics
  • Aging Research

Background:

  • Nuclear receptor subfamily 4 group A member 1 (Nr4a1) deficiency is linked to aging but its role in age-related hearing loss is unknown.
  • Investigating Nr4a1's impact on auditory function is crucial for understanding age-related hearing impairment.

Purpose of the Study:

  • To determine the effect of Nr4a1 deficiency on auditory function and cochlear structure.
  • To elucidate the molecular mechanisms underlying Nr4a1 deficiency-induced hearing loss.

Main Methods:

  • Utilized audiological assessments to evaluate hearing.
  • Employed immunofluorescence and transmission electron microscopy to examine cochlear sensory epithelium, cochlear nerve fibers (ANFs), and their subcellular structures.
  • Conducted transcriptome sequencing to analyze cochlear gene expression differences.

Main Results:

  • Nr4a1 knockout (KO) mice showed significant hearing impairment compared to controls.
  • Observed structural abnormalities including inner hair cell synapse damage, ANF demyelination, and mitochondrial changes in KO mice.
  • Identified differential gene expression in KO mice, correlating with cochlear immune cell infiltration.

Conclusions:

  • Nr4a1 deficiency exacerbates age-related hearing loss in C57BL/6N mice.
  • Structural damage to cochlear synapses and ANFs, alongside genetic and immune dysregulation, contributes to hearing impairment.
  • Nr4a1 plays a protective role in maintaining auditory function during aging.