Kanamycin ototoxicity in glutamate transporter knockout mice.
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.
Shimizu
Yoshitaka
Y
Department of Otolaryngology, Ehime University School of Medicine, Ehime, Japan.
Hakuba
Nobuhiro
N
Hyodo
Jun
J
Taniguchi
Masafumi
M
Gyo
Kiyofumi
K
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
D027322:Amino Acid Transport System X-AG; D009498:Neurotoxins; D018698:Glutamic Acid; D007612:Kanamycin