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

|
Figure 1. Separation of the reticular lamina between the second and
the third row of outer hair cells (arrows) following exposure to an
impulse noise. OHC1, OHC2 and OHC3 indicate the first, the
second and the third row of outer hair cells.
Figure 2. Increase in E-cadherin immunoreactivity (green fluorescence, arrows) in
the hair cells exhibiting condensed nuclei (red fluorescence, double-arrows) in a rat
cochlea following acoustic stress.
after the noise exposure, up-regulation
of gene expression was the dominant
change. As the time elapsed after the
noise exposure, downregulation of gene
expression became evident This
dynamic nature of gene expression
change is likely to be caused by the shift
of the triggering factors for cochlear
injury. The early damage is associated
with direct mechanical stress that occurs
during the period of acoustic
overstimulation, whereas the secondary
damage is associated with subsequent
cellular events, which include metabolic
disruption, oxidative stress, and ion
imbalance.
The changes in the expression levels of
adhesion genes are also related to the
level of hearing loss. Our correlation
analysis revealed that the expression
levels of several genes, including Sgce,
Sell, Itga5, Selp, and Cntn1, were related,
either positively or negatively, to the
level of the threshold shift of the
auditory brainstem response. These
genes may contribute to the individual
variation in the magnitude of cochlear
damage after acoustic trauma.
The changes in the expression patterns
of adhesion-related genes were found to
be spatially correlated with the
apoptotic activity of hair cells. We
observed an increased immunoreactivity
of E-cadherin, an adhesion
protein, in the circumferential rings of
the hair cells that exhibit an apoptotic
nuclear morphology, suggesting that the
change in E-cadherin expression is
associated with apoptotic degeneration
(Figure 2). Interestingly, certain hair
cells with increased E-cadherin
immunoreactivity have a relativelynormal
nuclear morphology, suggesting
that the E-cadherin change is an early
event of apoptosis.
Molecular mechanisms responsible for
adhesion disruption are not clear.
Matrix metalloproteinases (MMPs) are a
group of endopeptidases that participate
in the degradation of all components of
the extracellular matrix, including the
molecules responsible for cell-cell
junctions. These enzymes include
collagenases, gelatinases, stromelysins,
matrilysins, and other proteinases, each
with specialized cellular compartmentalization
and substrate specificity. We
therefore examined the involvement of
these proteins in noise-induced cochlear
damage. 7 Using a RNA-sequencing
technique, we identified multiple MMP
and related gene products, indicating
that MMPs are constitutively expressed
in the cochlea. Following exposure to a
broadband noise at 120 dB SPL, the
expression pattern of certain MMP
genes was altered. For example, the
expression of MMP7, which was
undetectable under the physiological
condition, became detectable in the
cochlear sensory epithelium. Moreover,
the expression level of intrinsic MMP
inhibitors (tissue inhibitors of
metalloproteinases) was altered after
noise exposure. These observations
suggest that MMPs are implicated in
cochlear responses to acoustic
overstimulation. Thus far, the biological
46 CANADIAN HEARING REPORT | REVUE CANADIENNE D’AUDITION