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UK funding (£600,764): Cholinergic efferent re-wiring of hair cells in the aging cochlea: understanding mechanisms and functional significance Ukri15 Jan 2020 UK Research and Innovation, United Kingdom
Overview
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Cholinergic efferent re-wiring of hair cells in the aging cochlea: understanding mechanisms and functional significance
| Abstract | Age-related hearing loss (ARHL) is the most common health condition in the elderly. Approximately half of adults in their 70's exhibit ARHL severe enough to affect communication. It is expected that approximately 14.5 million people in the UK will be affected by hearing loss by 2030, with ARHL being the single biggest cause. ARHL is a progressive disorder decreasing the ability to understand speech, especially in a noisy environment. ARHL is also associated with social isolation, depression, and an increased risk for neurodegenerative diseases. Although hearing aids and cochlear implants are beneficial, they cannot restore hearing especially if the cells in the ear are missing or do not function, which are both characteristic features in ARHL. The major obstacle preventing the development of new treatments for ARHL is a lack of understanding about why we progressively lose our sense of hearing with age, making it impossible to prevent, slowdown or even reverse ARHL. Sound is detected by extremely sensitive sensory cells named hair cells that are located inside a bony structure called the cochlea in the inner ear. Their name derives from the hair-like elements (stereocilia) that project from their apical surface. When sound enters the ear canal it produces minute vibrations of the stereocilia. These vibrations initiate the conversion of sound waves into an electrical current generated by the movement of charged ions through the opening of mechanically gated channels present in the hair cell stereocilia; a process known as mechano-electrical transduction. These electrical currents are a billion times smaller than those used to charge, for example, a mobile phone. Nevertheless, these tiny currents produced by the hair cells are sent to the brain via specialized sensory nerve fibres, allowing us to perceive sound such as speech and music. Crucial for normal hearing is the presence of motor nerve fibres, which are used by the brain to send instructions to hair cells and sensory nerve fibres (see above) in order to make a change in how they are functioning. For example, in the presence of a very loud noise, the motor nerve fibres reduce the activity of hair cells to avoid damage. Therefore, these motor neurons normally serve a protective role and generally help to keep the hair cells and sensory nerve fibres healthy. However, a recently discovered feature of ARHL is a change in the connections between the motor nerve fibres and hair cells, reverting back to an organization that is only present during pre-hearing stages of cochlear development. This change is peculiar since the motor nerve fibres in the immature cochlea do not serve a protective role, but instead influence the formation of the auditory pathway during early development. Currently, we do not know why the motor nerve fibres are changing in the aging cochlea. The hypothesis we plan to test in this grant is that the changes in the motor nerve fibre is an attempt to repair the faulty aged cochlea by "recapitulating" early development. In this project we will use aged mice showing signs of ARHL. However, working with aged mice is challenging and extremely costly because changes in the cochlea occur over long periods of time. Therefore, we will also use a few genetically modified mice that show the same changes in the motor nerve fibres as seen in aged mice, but within a much shorter time window. We will not only investigate when, how and why these changes in the organization of the motor nerve fibre occur, but also provide evidence about their functional role and whether the faulty cochlea has the potential to revert back to its normal mature structure following repair. This project will provide a better understanding of a crucial biological aspect associated with ARHL, which will contribute, in the future, to the identification of targetable genes allowing the development of diagnostic and therapeutic interventions in humans. |
| Category | Research Grant |
| Reference | BB/T004991/1 |
| Status | Active |
| Funded period start | 15/01/2020 |
| Funded period end | 14/01/2024 |
| Funded value | £600,764.00 |
| Source | https://gtr.ukri.org/projects?ref=BB%2FT004991%2F1 |
Participating Organisations
| University of Sheffield |
The filing refers to a past date, and does not necessarily reflect the current state. The current state is available on the following page: University of Sheffield, Sheffield.
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