Spiral ganglion neuron degeneration in mice with impaired potassium homeostasis of the cochlea

BARILA E; CARIGNANO C; RIAS E; DIONISIO, L.; AZTIRIA E; SPITZMAUL, G.

Cordoba

Congreso; XXXIII Congreso Anual SAN 2018; 2018

Sociedad Argentina de Investigación en Neurociencias (SAN)

Spiral ganglion neurons (SGNs) relay auditory information from the cochlea to central nuclei in the CNS. Their fibers receive inputs from inner hair cells (IHCs) which are the source of sound transduction. The voltage-activated potassium channel KCNQ4 is mainly expressed in Outer hair cells (OHCs), but also has been observed in IHCs and auditory pathway nuclei. Impaired activity of this channel causes OHCs degeneration, producing a sensorineural hearing loss, named DFNA2. The phenotype is initially explained by OHC death, however it progresses over time to profound deafness exceeding OHC function. Thus, it is postulated that a neuronal component could also be involved. We set out to study the role of SGNs in the progression of the hearing loss developed by KCNQ4 knock-out mice. We analyzed cochlear cell survival through time and localization using immunofluorescence on cochlear preparations. We found a significant decrease of SGN densities in basal portions of the cochlea as early as 40 weeks of age (W). By 52W the loss was also present in apical turns, and overall density of both regions decreased more than 50% by 60W. We also found loss of IHCs starting at 40W in basal turns, progressing towards the middle turn by 58W. Exploring mechanisms of cell death we found cleaved caspase 3 to be active on both OHCs and cells of SGNs. Our findings suggest a neuronal component involved in DFNA2-like deafness, and that apoptosis could be a mechanism active during cell degeneration.