LOWER DOSE OF AMINOGLYCOSIDE OTOTOXIC EXPOSURE CAUSES PRESYNAPTIC ALTERATIONS ASSOICATED WITH HEARING LOSS

(整期优先)网络出版时间:2014-01-11
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ObjectiveTostudypresynapticalternationsofcochlearribbonsarisingfromaminoglycosideototoxicstimuliinC57BL/6Jmice.MethodsAnimalswereinjectedwithlowdosegentamicin(100mg/kg/day)for14days,Fromthe14thto28thdays,themiceweremaintainedfreeofgentamicintreatment.Immunohisto-chemistrylabelingwasemployedtotraceRIBEYE,amajorpresynapticcomponmentofribbonsynapses.RIBEYE/CtBP2expressionlevelswereassessedandcomparedwithhearingthresholdshifts.Auditoryfunc-tionwasassessedbyauditorybrainstemresponses.Thestereociliaofouterhaircells(OHCs)andIHCswasexaminedbyscanningelectronmicroscopy(SEM).ResultsHearingthresholdswereelevatedwithpeakhearinglossobservedonthe7thdayaftergentamicinexposure,followedbyimprovementafterthe7thday.RIBEYE/CtBP2expressiondirectlycorrelatedwithobservedhearingthresholdshifts.Strikingly,wedidnotseeanyobviouschangesinstereociliainbothOHCsandIHCsuntilthe28thday.Mildchangesinstereocil-iawereonlyobservedinOHCsonthe28thday.ConclusionsThesefindingsindicatethatpresynapseco-chlearribbons,ratherthanstereocilia,maybesensitivetoaminoglycosideototoxicexposureinmicecochle-ae.ApatternofRIBEYE/CtBP2expressionchangesseemstoparallelhearingthresholdshiftsandsuggestspresynapticresponsepropertiestolowerdosageofaminoglycosideototoxicstimuli.