Biomarkers of Sensorineural Hearing Loss in the Peripheral and Central Auditory Pathway

Exposure to loud sound affects hair cells, the auditory nerve or central processing in the brain thereby producing sensorineural hearing loss (SNHL). This thesis aims to determine biomarkers of SNHL in rodents at the early stages (five days) after acoustic over exposure (AOE). Biomarkers of SNHL were characterized in the cochlea and in the cochlear nucleus, the first relay of the central auditory pathway integrating auditory and non-auditory projections. Wistar rats were here exposed for 6 hours to a loud (100 dB SPL) single tone (15 kHz). After five days, auditory brainstem response recordings showed increased hearing thresholds for frequencies exceeding 15 kHz. Electron microscopy performed at a similar time post AOE, showed a decreased number of myelinated auditory nerve fibres within the cochlea and a proportional increase of the number of cochlear unmyelinated auditory nerve fibres. Auditory nerve fibres project to the cochlear nuclei and after AOE, the central portion of the auditory nerve was characterized by a decreased diameter of its myelin sheath and a delocalization of Kv potassium channel subunits along nodal regions. Previous studies have shown that auditory nerve fibre terminals and non-auditory projections are characterized by VGLUT-1 and VGLUT-2 vesicular glutamate transporters respectively. Acoustic over-exposure led to a decreased expression of VGLUT-1 and an increased expression of VGLUT-2 transporters probably reflecting the auditory deficit and its compensation by non auditory projections respectively. The vestibular system relays information about the position of the head and the dorsal cochlear nucleus is involved in processing the localisation of sound in the vertical plane. The study demonstrates the presence of VGLUT-2 positive projections from the lateral vestibular nucleus to the dorsal cochlear nucleus. After AOE, the up-regulation of those VGLUT-2 vestibular projections suggests the involvement of vestibular compensation for the loss of VGLUT-1 mediated auditory inputs during SNHL. In summary, myelin and VGLUT transporters consist of biomarkers which could be acted upon during the early stages of SNHL following exposure to loud sound.