[Implication of mitochondrial apoptosis in neural degeneration of cochlea in a murine model for presbycusis].
OBJECTIVE
Pathologies of senescence, in particular those of neurosensory organs represent an important health problem. The improvement of the life expectation entails the fast increase of the frequency of the presbyacusis in the population. The biological and molecular causes of this degenerative pathology of the inner ear are linked to the disappearance of the sensory cells (inner and outer hair cells) and are associated to nervous damages of the spiral ganglion in the cochlea. We were interested in mechanisms causing the cochlear degeneration in a model of mouse CD 1 presenting prematurely auditive losses.


METHODS
We tried to correlate the evolution of the hearing and the appearance of apoptotic phenomena by marking with specific antibody, activated anti-caspase-3, in the cochlea during time. We studied the role and the involvement of proteins controlling the apoptosis as the P53 protein and from an energy point of view at the level of the mitochondria such as proteins of the Bcl-2 family and the cytochrome c in the various structures of the cochlea.


RESULTS
After implantation of electrodes for auditory nerve acoustic thresholds measurements, the audition of mice CD 1 presented a characteristic profile of hearing losses which begins in the high frequencies from the age of 1 month and which quickly evolves towards the low frequencies. The observation (between the 1st and 3rd month of age) of spiral ganglion cells revealed an unchanged number of cellular bodies of type 1 neurons, on the other hand a characteristic morphology of apoptosis of glial cells with the formation of apoptotic body was noted. Indeed, glial cells expressed activated caspase-3. Furthermore, this phenomenon seems to be under the control of the pro-apoptotic protein Bax by its overexpression and a increased release of the cytochrome c. This phenomenon was followed at 3 and 6 months by the disappearance of the outer hair cells by 9 and 48% respectively.


CONCLUSIONS
The apparition of the deafness in the murin model CD 1 allowed us to demonstrate that the degeneration of cochlear structure begins at the level of glial cells of the spiral ganglion from 3 months, followed thereafter by the deterioration of the nervous conduction between the spiral ganglion and the sensory cells. As a consequence, because of the impoverishment in nervous signals, the outer hair cells would begin to disappear during the 6th month. In conclusion, the understanding of the sequence and the cause of these mechanisms responsible for the neural degeneration and the loss of hearing could eventually, allow us to optimize the various treatments of the presbyacusis.
Riva
C
C
Laboratoire d'Otologie Neuro-Otologie et Microendoscopie Université de la Méditerranée Aix-Marseille II, IFR Jean Roche, Faculté de Médecine Nord, Boulevard Pierre Dramard, F-13916 Marseille cedex 20, France. riva-lavieille.c@jean-roche.univ-mrs.fr
Longuet
M
M
Lucciano
M
M
Magnan
J
J
Lavieille
J P
JP
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D003051:Cochlea / Q000378:metabolism / Q000648:ultrastructure*; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure*; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology*; D011304:Presbycusis / Q000378:metabolism / Q000473:pathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C435486:Bmf protein, mouse; D016159:Tumor Suppressor Protein p53