Role of the adaptive immune system in spiral ganglion neuron degeneration after deafening

Hearing impairment is the most common sensory abnormality. Loss of the auditory receptor cells in our ears is one of the most common causes of deafness. The auditory function of these receptors can be replaced with a cochlear implant. However, the neurons that connect these receptors to brain, which we call spiral ganglion neurons (SGN), die after deafening, in human subjects and in animal models. This potentially can impair the function of a cochlear implant. Various hypotheses have been proposed to explain this phenomenon. In recent years, evidence has been accumulating that after loss of the auditory receptor cells, there is significant inflammation in our ear, in the vicinity of the neurons. A new, ‘neuroinflammation hypothesis’ has emerged for the degeneration of these neurons. In this thesis, I have examined the question of whether this post-deafening inflammation in the ear is neurotoxic. In animal model, we found that it is neurotoxic. The immune response consists of both ‘innate’ or ‘adaptive’ responses. The ‘innate’ immune response is non-specific against any insult whereas the ‘adaptive’ immune response specifically attacks some cells or molecules. We hypothesized that this neurotoxic inflammation is an ‘adaptive’ response that is directed towards some molecular component(s) of the SGNs or cells that are necessary for their survival. Our experiments demonstrate that this is the case. This knowledge will help us to improve the function of cochlear implants and will have a significant impact in our understanding of interaction between the nervous system and the immune system.