Saynpatic mechanisms of noise-induced hearing loss
by Mauro Alfonso Malpede
Date of Examination:2023-04-25
Date of issue:2024-04-19
Advisor:Dr. Tina Pangrsic
Referee:Dr. Tina Pangrsic
Referee:Prof. Dr. Silvio Rizzoli
Persistent Address:
http://dx.doi.org/10.53846/goediss-10455
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Abstract
English
Noise-induced hearing loss (NIHL) is a form of acquired hearing impairment, caused by exposure to loud noise, that damages the delicate inner ear structures, possibly including the neural connections between the Inner Hair Cells (IHCs) and Spiral Ganglion Neurons (SGNs). The symptoms of NIHL depend on the nature of exposure and may include difficulty hearing in noise, understanding speech, muffled speech, or tinnitus. In severe cases, the hearing loss can be profound and strongly affect the overall quality of life. Currently, there is no causative treatment and cure for NIHL. The different manifestations of synaptic pathologic changes and the underlying synaptic mechanisms are not yet well understood. Yet, such knowledge could guide development of novel therapies, which was in focus of my thesis. In my PhD project, I investigated the effects of noise exposure under volatile anesthesia using two levels of noise stimulation. I developed a new mouse model of noise-induced synaptopathy that is mild to moderate and involves partially delayed loss of ribbon synapses that develops in conditions of mild or no immediate loss of hearing sensitivity. Patch-clamp recordings from basal inner hair cells (IHCs) immediately post noise exposure showed a temporary increase in the efficiency of IHC exocytosis upon noise exposure causing a larger temporary hearing threshold shift. Two weeks after exposure, the hearing sensitivity was mildly increased for both noise intensities tested. Despite aprox. 20% loss or ribbon synapses in the IHCs of the basal cochlea, the whole-cell calcium current amplitudes and exocytosis were not affected. These findings indicate that acute noise exposure enhances IHCs exocytosis at the remaining ribbons or possibly extrasynaptically, which should be studied in more detail in the future. Furthermore, the use of the anesthetic isoflurane, which was previously shown to protect against noise-induced reduced hearing sensitivity, was discovered to provide partial, but not complete protection to ribbon synapses. However, my work further revealed that a moderate loss of ribbon synapses can still occur even in the presence of very mild immediate hearing threshold shift, previously not shown to permanently harm synapses. In conclusion, this study has provided new insights into the manifestations of noise-induced synaptopathy and established a new foundation for future research in this field, which could lead to the development of new therapies to protect auditory systems from damage caused by loud noise.
Keywords: Noise-induced hearing loss (NIHL).; Inner Hair Cells (IHCs); Spiral Ganglion Neurons (SGNs); Synaptopathy; Ribbon synapses; Isoflurane; Exocytosis; Patch-clamp recordings; Therapeutic development; Auditory system protection
