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Title: Mitochondrial function in the neonatal rat cochlea
Author: Mann, Zoe Francesca
ISNI:       0000 0004 2670 7450
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2008
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The cochlea is a specialised structure that contains the cells responsible for transducing mechanical sound stimuli into neural code within the auditory nerve. Mutations in the mitochondrial genome have been associated with hearing loss, suggesting that they play a key role in cochlear physiology. Alongside ATP production, mitochondria are also intimately involved in processes such as calcium homeostasis and the regulation of cell death. The precise role for mitochondria in inner ear physiology is at present poorly defined. I used neonatal cochlear explants and confocal microscopy to study aspects of mitochondrial physiology. The dye TMRM was used to investigate differences in A j/mt between basal and apical inner (IHC) and outer (OHC) hair cells and supporting cells. Data reveal a base-to-apex difference in mitochondrial function specific to inner hair cells. Mitochondrial function was investigated further using the endogenous autofluorescence of NADH and flavoproteins and revealed a base-to-apex difference in cell redox state, again in the IHCs but not OHCs. Differences in intracellular metabolism were also investigated using fluorescence lifetime imaging of NAD(P)H and revealed metabolic differences between OHCs and supporting cells consistent with a metabolism that is more glycolytic in supporting cells and more oxidative in OHCs. 9+ The role of mitochondria in cochlear Ca homeostasis was also investigated. The amplitude and spatiotemporal properties of intercellular Ca waves initiated by ATP 9+ 9+ were studied. Blocking mitochondrial Ca ( Ca mt) uptake using Ru360 increased the wave amplitude, propagation velocity and extent of spread in cochlear supporting cells, 94- showing that mitochondrial Ca buffering plays a role in shaping calcium signals in the cochlea. 9+ 9+ Finally, neomycin was used to investigate Ca c and Ca mt during neomycin toxicity. 94- Neomycin induced a rapid bi-phasic response in OHC Ca c leading to cell loss of A /mt and cell permeabilsation, which correlated with ATP-dependent intercellular Ca waves in the surrounding supporting cells.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available