Morphological and molecular changes in the inner hair cell region of the rat cochlea after amikacin treatment.
This study investigates the morphological and molecular changes that occur in the inner hair cell area of the rat cochlea following aminoglycoside treatment. Rats were injected daily with 500 mg/kg of amikacin between postnatal day 9 (PND9) and PND16. Cochleae were examined at PND16 to PND120 using both scanning and transmission electron microscopy and molecular fluorescent labeling. The inner hair cells showed obvious signs of apoptosis in response to amikacin treatment and most of them were missing by one week after the end of the aminoglycoside exposure period. Concomitantly, the epithelium became scarred as the surrounding supporting cells expanded and filled the space vacated by the missing IHCs. The mid-basolateral region of these modified supporting cells was surrounded by many afferent and efferent terminals. However, these cells expressed neither calbindin nor SNAP25, proteins that are both expressed by IHCs in the normal, untreated organ of Corti in the rat. In addition, these supporting cells remained attached to the basal lamina by a thin cytoplasmic process. The supporting cells surrounding the inner hair cells therefore appear unable to convert directly into inner hair cells following aminoglycoside induced hair-cell loss but may be able to provide trophic support for the remaining afferent and efferent neurites.
Lenoir
M
M
INSERM UR254, Université Montpellier I, Faculté de Médecine, Montpellier, France.
Daudet
N
N
Humbert
G
G
Renard
N
N
Gallego
M
M
Pujol
R
R
Eybalin
M
M
Vago
P
P
D000199:Actins / Q000096:biosynthesis; D000583:Amikacin / Q000633:toxicity*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D017209:Apoptosis; D064026:Calbindins; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D007760:Labyrinth Supporting Cells / Q000166:cytology; D008565:Membrane Proteins; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D064030:S100 Calcium Binding Protein G / Q000096:biosynthesis; D050825:Synaptosomal-Associated Protein 25
D000199:Actins; D000900:Anti-Bacterial Agents; D064026:Calbindins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D064030:S100 Calcium Binding Protein G; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D000583:Amikacin