Detailed examination of neurodegeneration in peripheral and central structures of the ascending auditory pathway after noise-induced hearing loss in adult mice

• Applicant: Dr. Moritz Gröschel
• Subject Area: Otolaryngology, Phoniatrics and Audiology
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 256760627

It is the aim of the present project to examine the anatomical consequences of noise trauma in the peripheral and central auditory system in normal hearing, adult mice using histological and immunohistochemical techniques. First, investigations should focus on the dimensions of neurodegeneration in key structures of central auditory processing. Second, the course of time of these processes is to be highlighted in detail. The intended studies are based on our recently published research data on central effects of noise-induced hearing loss in the auditory system. Despite physiological alterations of neuronal activity, we have shown that neuroplastic and degenerative processes are present to a large extend. Our results showed for the first time an immediate loss of neurons in auditory brain structures after noise exposure, followed by a dramatic reduction in cell densities within the next days. Initial studies on the underlying mechanisms lead to the assumption that apoptosis plays a key role in this pathogenesis. Due to the findings that a single noise trauma has such a large impact on central auditory structures within a short period of time, it became highly important to perform further experiments to get more detailed insights into the underlying mechanisms within the entire ascending auditory pathway. Therefore, immunohistochemical methods should be used to detect specific cell death mechanisms (TUNEL-staining). Moreover, basic morphological changes will be demonstrated by histological standard methods (e.g. HE staining). In particular, observations of the time-dependent development of pathologies will be carried out to give information about the time frame for the possibility of (e.g. pharmacological) intervention to reduce or prevent degeneration of neuronal tissue. Since recent studies showed that long-term neurodegeneration also occurs upon low-intensity sound exposure (<90 dB SPL), different models of acoustic trauma should be tested in the present experimental design. The pathological impact in these previous investigations (reduction of neuronal tissue, progressive hearing loss) was comparable to those occurring after noise trauma with high sound pressure levels, but was delayed in time up to a few months. However, using the specified methods, primary effects might be detected already at a very early point in time. This offers the opportunity for a specific intervention, leading to neuroprotection and therefore hearing preservation. From this point of view, the present study is, beyond its significance for basic auditory research, of high practical relevance, as it provides insight into the mechanisms and the chronology of noise-induced neuronal pathologies, leading to a better understanding of several clinical audiological phenomena. Based on these findings, it should be possible to develop treatment strategies which preserve patients from a drastic deterioration of central nervous auditory processing quality (central hearing loss).

• DFG Programme: Research Grants
• Participating Persons: Privatdozent Dr. Dietmar Basta; Professor Dr. Arneborg Ernst