The His723Arg (H723R) mutation in , encoding pendrin, is the most prevalent mutation in East Asia, resulting in DFNB4, an autosomal recessive type of genetic hearing loss. Although the main pathological mechanism of H723R was identified as a protein-folding defect in pendrin, there is still no curative treatment for associated hearing loss. Here, we show that H723R-pendrin expression and activity are rescued by activation of the chaperonin DNAJC14. , DNAJC14 was activated via Japanese encephalitis virus (JEV) inoculation, and toxin-attenuated JEV rescued the surface expression and anion exchange activity of H723R-pendrin. Human H723R-pendrin transgenic mice (hH723R Tg) were established in a mouse knockout background, in which only hH723R-pendrin was expressed in the inner ear (Pax2-Cre dependent) to mimic human DFNB4 pathology. Crossing hH723R Tg with DNAJC14-overexpressing mice resulted in reduced cochlear hydrops and more preserved outer hair cells in the cochlea compared to those in hH723R Tg mice. Furthermore, the stria vascularis and spiral ligament were thicker and KCNJ10 expression was increased with DNAJC14 overexpression; however, hearing function and enlarged endolymphatic hydrops were not recovered. These results indicate that DNAJC14 overexpression ameliorates the cochlear degeneration caused by misfolded pendrin and might be a potential therapeutic target for DFNB4.
In sensory perception, stochastic resonance (SR) refers to the application of noise to enhance information transfer, allowing for the sensing of lower-level stimuli. Previously, subjective-assessments identified SR in vestibular perceptual thresholds, assessed using a standard two alternative (i.e.
To encode continuous sound stimuli, the inner hair cell (IHC) ribbon synapses utilize calcium-binding proteins (CaBPs), which reduce the inactivation of their Ca1.3 calcium channels. Mutations in the gene underlie non-syndromic autosomal recessive hearing loss DFNB93.
Neural diversity can expand the encoding capacity of a circuitry. A striking example of diverse structure and function is presented by the afferent synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in the cochlea. Presynaptic active zones at the pillar IHC side activate at lower IHC potentials than those of the modiolar side that have more presynaptic Ca channels.
The current understanding of the human auditory system has been primarily based on studies using animal and cellular models. Organoids have been used to simulate cochlear structures and replicate cochlear functions. However, the physical and chemical cues required to control the development of cochlear organoids accurately remain poorly understood, limiting research advances on cochlea-on-a-chip systems.
Imperceptible noisy galvanic vestibular stimulation (nGVS) improves standing balance due to the presence of stochastic resonance (SR). There is, however, a lack of consensus regarding the optimal levels and type of noise used to elicit SR like dynamics. We aimed to confirm the presence of SR behavior in the vestibular system of young healthy adults by examining postural responses to increasing amplitudes of white and pink noise stimulation scaled to individual cutaneous perceptual threshold.
