Volume 8 Issue 1 (pdf) - Andrew John Publishing Inc
Volume 8 Issue 1 (pdf) - Andrew John Publishing Inc
Volume 8 Issue 1 (pdf) - Andrew John Publishing Inc
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esearCh and deVeLoPMent foCus |<br />
Noise-Induced Cochlear Damage:<br />
Changes In Cell Adhesion Contributes to Sensory Cell Death<br />
By Bo Hua Hu, PhD<br />
bhu@buffalo.edu<br />
Noise-induced hearing loss is a<br />
common cause of acquired sensory<br />
hearing loss in the adult population.<br />
Functionally, acoustic overstimulation<br />
compromises hearing sensitivity and<br />
reduces the temporal and frequency<br />
resolutions. Pathologically, acoustic<br />
overexposure damages cochlear<br />
structures and causes sensory cell death.<br />
Because sensory cells in the mammalian<br />
cochlea are unable to regenerate once<br />
they die, loss of these cells results in<br />
permanent hearing loss. To prevent such<br />
loss, it is essential to understand the<br />
biological and molecular mechanisms of<br />
sensory cell degeneration, so that<br />
effective treatments can be developed.<br />
Recent studies have shown that sensory<br />
cell degeneration is a complex<br />
molecular process, involving multiple<br />
signaling pathways. Among these<br />
pathways, molecular events that are<br />
associated with apoptotic cell death<br />
have received a great attention.<br />
Apoptosis is an active type of cell<br />
degeneration that requires a sustained<br />
energy supply during the early phase of<br />
About the Author<br />
Bo Hua Hu is with the Center for Hearing and<br />
Deafness, State University of New York at Buffalo.<br />
Buffalo, NY.<br />
cell death. In the cochlea, apoptosis is<br />
triggered by exposure to a high level of<br />
noise exposure and occurs primarily at<br />
the initial phases of cochlear damage. 1<br />
Apoptosis has been linked to both<br />
intrinsic and extrinsic signaling<br />
pathways. 2 However, how these<br />
signaling pathways are activated is not<br />
clear.<br />
Cell-cell junctions are an important<br />
element for maintenance of the<br />
structural integrity of tissues. In the<br />
cochlea, cell adhesion is organized<br />
through tight, gap, and adherens<br />
junctions, and through desmosomes<br />
and focal adhesions. These junctions<br />
play an essential role in the maintenance<br />
of structural integrity, cellular function,<br />
and signal transduction of sensory cells<br />
and supporting cells.<br />
Cell-cell junctions are also a major target<br />
of acoustic overstimulation. Morphological<br />
analyses of cochlear structures<br />
have revealed structural defects in cell<br />
junctions, 3,4 such as the detachment of<br />
sensory cells from their anchorage and<br />
the splitting of the reticular lamina at<br />
cell-cell junctions (Figure 1). A recent<br />
observation from our laboratory has<br />
shown that even at the situation in<br />
which the general structure of the organ<br />
of Corti is preserved, an increase in the<br />
permeability to macromolecules can<br />
take place in the intracellular junctions. 5<br />
These observations led us to hypothesize<br />
that damage to cell junctions can serve<br />
as a trigger event for the generation of<br />
acute sensory cell apoptosis.<br />
To investigate the molecular changes<br />
associated with cell junction disruption,<br />
we recently examined the expression<br />
pattern of cell adhesion-related genes in<br />
the cochlear sensory epithelium. 6<br />
Under the normal condition, multiple<br />
adhesion-related genes are constitutively<br />
expressed in the cochlear sensory<br />
epithelium. The highest-expressed<br />
genes include Ctnnb1, Catna1, Thbs1,<br />
and Lamb2. Interestingly, the expression<br />
levels of many genes differ between the<br />
apical and basal sections of the organ of<br />
Corti. This difference may contribute to<br />
the difference in the noise susceptibility<br />
of the sensory cells between these two<br />
sections of the organ of Corti.<br />
Following exposure to a broadband<br />
noise at 120 dB SPL (sound pressure<br />
level) for 2 hours, we found a significant<br />
change in the expression levels of<br />
multiple adhesion genes. Importantly,<br />
these expression changes occurred in a<br />
time-dependent fashion. Immediately<br />
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