dc.contributor.advisor |
Dr Srdjan Vlajkovic |
en |
dc.contributor.author |
Dharmawardana, Nuwan Shyanaka |
en |
dc.date.accessioned |
2010-09-30T03:31:56Z |
en |
dc.date.available |
2010-09-30T03:31:56Z |
en |
dc.date.issued |
2008 |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/5997 |
en |
dc.description |
Full text is available to authenticated members of The University of Auckland only. |
en |
dc.description.abstract |
Extracellular adenosine acting via adenosine receptors (A1, A2A, A2B and A3) plays
neuromodulatory role in many tissues. Adenosine kinase (AdK) is the most abundant
nucleoside kinase that phosphorylates intracellular adenosine to AMP and is a key regulator
of adenosine concentrations on both sides of the cell membrane. Here, we report the AdK
distribution in the rat cochlea at mRNA and protein levels and provides evidence that AdK
inhibition may be a pharmacological tool in mediating cochlear recovery from injury.
Adult Wistar rats were exposed to broadband or narrow band noise for 24 hours at 90 dB,
100 dB and 110 dB sound pressure level (SPL) and tissues were collected after 1 hour or 3
days following noise exposure. They were compared to control tissues that were not exposed
to noise (non-noise controls). Noise presented at 90 dB and 100 dB represents the model of
transient hearing loss (temporary threshold shift), whilst exposure to 110 dB SPL induces
permanent hearing loss. AdK transcript levels were determined in the noise-exposed
cochleae and compared to controls. Only the cochleae exposed to 90 dB SPL demonstrated
increased AdK transcript levels after 1 hour of recovery, whilst AdK expression levels were
unchanged in other cochleae. Semi-quantitative analysis of AdK protein levels was carried
out on cryo-sectioned and immunolabelled cochlear tissues examined under the confocal
microscope. The intensity of immunostaining was measured using average pixel intensity in
discrete regions of the cochlea. Immunofluorescence analysis demonstrated initial increase
in AdK in the cochleae of animals exposed to high level noise (110 dB SPL), but transient
increase in AdK levels returned to basal levels after 3 days of post-noise recovery.
Immunolabelling with caspase-3 and nitrotyrosine demonstrated the extent of tissue damage
and oxidative stress in the noise-exposed cochleae.
In other studies, Wistar rats were exposed to 110 dB SPL noise at various frequency bands
for different durations. Systemic intra-peritoneal administration of ABT-702, an AdK inhibitor,
demonstrated partial recovery of hearing thresholds in animals exposed to noise for 4 hours,
whilst that effect was lost in animals exposed to noise for 24 hours. Therefore, this study
provides the first evidence that inhibition of AdK following intense noise exposure can
influence the development of noise induced cochlear damage and may thus be a potential
treatment strategy to ameliorate noise induced hearing loss. |
en |
dc.language.iso |
en |
en |
dc.publisher |
ResearchSpace@Auckland |
en |
dc.relation.ispartof |
Masters Thesis - University of Auckland |
en |
dc.relation.isreferencedby |
UoA1901383 |
en |
dc.rights |
Restricted Item. Available to authenticated members of The University of Auckland. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.rights.uri |
http://creativecommons.org/licenses/by-nc-sa/3.0/nz/ |
en |
dc.subject |
adenosine |
en |
dc.subject |
adenosine kinase |
en |
dc.subject |
cochlear |
en |
dc.subject |
noise |
en |
dc.subject |
hearing loss |
en |
dc.title |
The role of adenosine kinase in noise induced hearing loss |
en |
dc.type |
Thesis |
en |
thesis.degree.grantor |
The University of Auckland |
en |
thesis.degree.level |
Masters |
en |
dc.rights.holder |
Copyright: The author |
en |
dc.identifier.wikidata |
Q112877287 |
|