Volume 8 Issue 1 (pdf) - Andrew John Publishing Inc

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