The Journal of Neuroscience, December 1, 2000, 20(23):8750-8753
Exacerbation of Noise-Induced Hearing Loss in Mice Lacking the
Glutamate Transporter GLAST
Nobuhiro
Hakuba1,
Kenichiro
Koga1,
Kiyofumi
Gyo1,
Shin-ichi
Usami2, and
Kohichi
Tanaka3
1 Department of Otolaryngology, Ehime University School
of Medicine, Ehime 791-0295, Japan, 2 Department of
Otorhinolaryngology, Hirosaki University School of Medicine, Hirosaki
036-8562, Japan, and 3 Department of Molecular
Neuroscience, Medical Research Institute, Tokyo Medical and Dental
University, Bunkyo-ku, Tokyo 113-8519, Japan
Acoustic overstimulation is one of the major causes of hearing
loss. Glutamate is the most likely candidate neurotransmitter for
afferent synapses in the peripheral auditory system, so it was proposed
that glutamate excitotoxicity may be involved in noise trauma. However,
there has been no direct evidence that noise trauma is caused by
excessive release of glutamate from the inner hair cells (IHCs) during
sound exposure because studies have been hampered by powerful glutamate
uptake systems in the cochlea. GLAST is a glutamate transporter highly
expressed in the cochlea. Here we show that after acoustic
overstimulation, GLAST-deficient mice show increased accumulation of
glutamate in perilymphs, resulting in exacerbation of hearing loss.
These results suggest that GLAST plays an important role in keeping the
concentration of glutamate in the perilymph at a nontoxic level during
acoustic overstimulation. These findings also provide further support
for the hypothesis that IHCs use glutamate as a neurotransmitter.
Key words:
glutamate transporter; excitotoxicity; noise trauma; inner hair cell; knock-out mouse; supporting cell
Copyright © 2000 Society for Neuroscience 0270-6474/00/20238750-04$05.00/0
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