Thesis
The adaptive immune response: a potential cause of spiral ganglion neurodegeneration after deafening
University of Iowa
Master of Science (MS), University of Iowa
Spring 2024
DOI: 10.25820/etd.007316
Abstract
Sensorineural hearing loss is one of the most prevalent sensory deficits in humans today and it is commonly caused by the damage of auditory sensory cells (hair cells). Cochlear implants can restore the function of hair cells and rescue hearing loss but the efficacy of cochlear implants requires a normal and functional population of auditory neurons (spiral ganglion neurons). However, the death or damage of hair cells leads to the degeneration of spiral ganglion neurons (SGNs) in humans and most animal models. The reason and mechanism of SGN degeneration is unclear but recent studies have suggested that neuroinflammation plays a role. For immune responses involved in SGN degeneration, current studies mostly focus on the innate immune response and the adaptive immune has been poorly studied. Previous studies in our lab revealed that the immune response is neurotoxic and the adaptive immune response plays a critical role in SGN degeneration after deafening. An important component of the adaptive immune response, the MHCII, is shown to be causal in SGN death. Here, I show that the MHCII expression increases after hair cell loss in the cochlea and the upregulation of MHCII occurs before SGN degeneration. Besides that, the elimination of T cells does not prevent SGN death after deafening in rats. These results suggest that the MHCII-mediated antigen presentation plays an important role in SGN death, but T lymphocytes might not contribute to SGN degeneration.
Details
- Title: Subtitle
- The adaptive immune response: a potential cause of spiral ganglion neurodegeneration after deafening
- Creators
- Zhenshen Zhang
- Contributors
- Steven H Green (Advisor)Michael E Dailey (Committee Member)Noah S Butler (Committee Member)
- Resource Type
- Thesis
- Degree Awarded
- Master of Science (MS), University of Iowa
- Degree in
- Integrated Biology
- Date degree season
- Spring 2024
- DOI
- 10.25820/etd.007316
- Publisher
- University of Iowa
- Number of pages
- ix, 51 pages
- Copyright
- Copyright 2024 Zhenshen Zhang
- Language
- English
- Date submitted
- 04/23/2024
- Description illustrations
- illustrations, tables, graphs
- Description bibliographic
- Includes bibliographical references (pages 49-51).
- Public Abstract (ETD)
- Hearing loss is the most common sensorineural deficit and it is usually caused by the death of auditory sensory cells (hair cells). Cochlear implants can replace these sensory cells to regain the ability of sound detection. However, neurons that connect sensory cells to the brain will degenerate when auditory sensory cells die and impair the function of cochlear implants. The cause of neurodegeneration after trauma is unknown but recent studies suggest that immune response, especially adaptive immunity, contributes to death of auditory neurons. In my thesis, I show that the expression of a marker for adaptive immune response: MHCII molecules, increases post-deafening. The increased expression of MHCII happens before neuronal death therefore the unregulated MHCII expression is not a consequence of SGN death and could be causal to SGN degeneration. Besides that, my work suggests that macrophage is associated with SGN survival, but T lymphocytes do not play a role in SGN death. This finding helps us understand the neurodegenerative process in the ear, especially the effect of neuroinflammation on hearing.
- Academic Unit
- Biology
- Record Identifier
- 9984647645402771
Metrics
20 Record Views