title: Kanamycin ototoxicity in glutamate transporter knockout mice.
abstract: Glutamate-aspartate transporter (GLAST), a powerful glutamate uptake system, removes released glutamate from the synaptic cleft and facilitates the re-use of glutamate as a neurotransmitter recycling system. Aminoglycoside-induced hearing loss is mediated via a glutamate excitotoxic process. We investigated the effect of aminoglycoside ototoxicity in GLAST knockout mice using the recorded auditory brainstem response (ABR) and number of hair cells in the cochlea. Kanamycin (100 mg/mL) was injected directly into the posterior semicircular canal of mice. Before the kanamycin treatment, there was no difference in the ABR threshold average between the wild-type and knockout mice. Kanamycin injection aggravated the ABR threshold in the GLAST knockout mice compared with the wild-type mice, and the IHC degeneration was more severe in the GLAST knockout mice. These findings suggest that GLAST plays an important role in preventing the degeneration of inner hair cells in aminoglycoside ototoxicity.
authors.affiliation: Department of Otolaryngology, Ehime University School of Medicine, Ehime, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Hakuba
authors.forename: Jun
authors.initials: J
authors.lastname: Hyodo
authors.forename: Masafumi
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Gyo
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000235:genetics*; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects / Q000502:physiology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology; D007612:Kanamycin / Q000633:toxicity*; D051379:Mice; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D009498:Neurotoxins / Q000633:toxicity*; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics
chemical_list: D027322:Amino Acid Transport System X-AG; D009498:Neurotoxins; D018698:Glutamic Acid; D007612:Kanamycin