Pathophysiological processes underlying hidden hearing loss revealed in Kcnt1/2 double knockout mice

Area of Science:

• Otolaryngology
• Neuroscience
• Gerontology

Background:

• Presbycusis (age-related hearing loss) is prevalent in older adults.
• Hidden hearing loss, difficulty understanding speech in noise despite normal hearing, may precede overt hearing loss.
• Pathological mechanisms of hidden hearing loss are poorly understood, hindering treatment development.

Purpose of the Study:

• To investigate the pathological mechanisms underlying hidden hearing loss.
• To examine the transition from hidden to overt age-related hearing loss.
• To identify early molecular and cellular changes in the cochlea.

Main Methods:

• Utilized Kcnt1/2 double knockout mice as a model for hidden hearing loss.
• Employed transcriptomic profiling to analyze gene expression.
• Conducted morphological and functional assessments of cochlear structures.

Main Results:

• Hidden hearing loss is associated with altered proteostasis in cochlear sensorineural structures before observable pathology.
• Kcnt1/2 knockout mice show increased susceptibility to noise-induced and age-related hearing loss.
• Identified early pathophysiological changes linked to the progression of hearing impairment.

Conclusions:

• This study provides the first insights into the pathophysiology of early-stage hearing loss.
• Findings highlight proteostasis as a key process in hidden hearing loss.
• Results guide future research into pharmaceutical strategies for preventing or slowing age-related hearing loss.