New insights into glutamate ototoxicity in cochlear hair cells and spiral ganglion neurons.
CONCLUSIONS
Excess glutamate (Glu) exposure (20 mM) in the cochlear perilymph affects the physiological function of outer hair cells (OHCs) within a 2 h period and induces apoptosis in the modiolus spiral ganglion neurons (SGNs) in an apoptosis-inducing factor (AIF)-dependent manner.


OBJECTIVE
To determine whether high-dose Glu affects the function of OHCs and whether it induces AIF- and caspase-3-dependent apoptosis in the cochlear SGNs.


METHODS
Perilymphatic perfusions of Glu (20 mM) and artificial perilymph (AP) solutions were performed in adult guinea pig cochleae. Both cochlear microphonics (CM) and electrical auditory brainstem response (eABR) were measured before and 2 h after perfusions. The hair cell morphologies were examined using transmission electron microscopy. The expression of two apoptotic indicators, AIF and caspase-3, was examined 8 h after perfusions.


RESULTS
In contrast to AP perfusions, the perfusion of 20 mM Glu caused significant reduction in the CM and eABR amplitudes. Inner hair cells (IHCs) after Glu perfusion were deformed and exhibited vacuolization in the postsynaptic region, whereas the OHC system appeared unaffected. AIF expression was detected in the nuclei of SGNs 8 h after Glu exposure, but the expression of caspase-3 was not shown in any cochlear tissues.
Lu
Haitao
H
Department of Otolaryngology, Union Hospital, Huazhong Science and Technology University, Wuhan, China.
Wang
Xiang
X
Sun
Wenyan
W
Hu
Yao
Y
Gong
Shusheng
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D003055:Cochlear Microphonic Potentials / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D018698:Glutamic Acid / Q000633:toxicity*; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000187:drug effects* / Q000473:pathology; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects* / Q000473:pathology; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D010477:Perfusion; D010498:Perilymph; D013136:Spiral Ganglion / Q000187:drug effects* / Q000473:pathology
D051033:Apoptosis Inducing Factor; D018698:Glutamic Acid; D053148:Caspase 3