The expression of apoptosis-related proteins in the aged cochlea of Mongolian gerbils.
OBJECTIVE
Apoptotic changes have been reported in the aged gerbil cochlea and are speculated to be one of the principal causes of presbyacusis. The objective of the study was to determine the underlying mechanism of apoptotic change in the aged gerbil cochlea.


METHODS
Prospective controlled animal study.


METHODS
We examined the tissue distribution of bcl-2, bax, caspase-3p20, and caspase-3p32 using immunohistochemical techniques in the young and aged gerbil cochlea, together with the measurement of the distortion product of otoacoustic emission (DPOAE).


RESULTS
Aged gerbils showed a significant reduction of the DPOAE amplitude as compared with that of the young gerbils, suggesting a disturbance of the auditory function in the aged cochlea. There was a significant decrease in the number of bcl-2-positive cells in the aged gerbils. The expression of bax in the aged group was slightly increased but did not significantly differ from that in the young gerbils. A significantly increased number of caspase-3p20-positive cells was observed in the organ of Corti, spiral ganglion, and lateral wall of cochlea in the aged gerbils as compared with those of the young gerbils. There was no significant difference in the expression levels of caspase-3p32 between the young and aged groups. In the aged cochlea, the degree of deterioration of DPOAE responses was compatible with those of both the reduction of bcl-2 and the activation of caspase-3p20.


CONCLUSIONS
These data suggest that the suppression of bcl-2 protein expression may lead to apoptosis-induced presbyacusis through activation of caspase-3 in the aged gerbil cochlea.
Department of Otorhinolaryngology-Head and Neck Surgery, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
S A
SA
Alam
T
T
Oshima
M
M
Suzuki
T
T
Kawase
T
T
Takasaka
K
K
Ikeda
D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000032:analysis*; D003051:Cochlea / Q000473:pathology*; D005849:Gerbillinae; D017084:Otoacoustic Emissions, Spontaneous / Q000502:physiology; D011304:Presbycusis / Q000473:pathology*; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D051028:bcl-2-Associated X Protein
D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D020169:Caspases