Analysis of otospiralin down-regulation and acoustic damage to organ of Corti in guinea pig.

Noise over-stimulation induces or influences molecular pathways in the cochlea. One approach to the identification of the components of these pathways is to examine genes and proteins that change after the different types and levels of stress. Quantitative RT-PCR was used to understand if there were changes in the expression of proteins not directly involved in perception of sound consequently to white noise administration. We found a downregulation of mRNA level of otospiralin, a protein expressed by fibrocytes in the cochlea of guinea pigs, after white noise over-stimulation at 108 dB SPL. This level of noise caused a temporary threshold shift (TTS) after 2h and a permanent threshold shift (PTS) after 5h. This could indicate that otospiralin is directly involved in ion homeostasis in endolimph. On the other hand one cannot exclude that the down-regulation of otospiralin could alter the fibrocytes themselves and indirectly perturb hair cells metabolism. By using in situ hybridization we have showed that there was not relevant change in cell types expressing otospiralin after noise stress. In order to determine whether there was damage together with TTS, we have examined, by SEM analysis, the hair cells fate in the organ of Corti after exposure to white noise. After 2 h of treatment the damage is mainly evident to the 2nd and 3rd rows of outer hair cells whereas inner hair cells are no compromised. Apical turn outer hair cells are more vulnerable to damage than basal ones. After 1 month from over-stimulation, in agreement with the measure of the TTS, there is a recovery only in the specimens treated for 2 h. We can conclude that, consequently to the administration of white noise for 2 h, the sensorial epithelium is able to recover the damage because the cells are only weakly damaged. On the contrary white noise over-stimulation for 5h, lead to the death of sensorial cells, probably for ROS induced apoptosis, and the epithelium is no more able to recover the damage.