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Study on Role of Glutamate and its Protection of Neural Toxity in Inner Ear Damage

谷氨酸在内耳损伤中的作用及其对神经毒性的保护作用研究

基本信息

批准号：
11671684
负责人：
GYO Kiyofumi
金额：
$ 2.24万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671684/
关键词：
transient cochlear ischemia glutamate excitotoxicity inner hair cell damage delayed neuronal death hypothermic therapy glutamate transporter sudden deafness noise induced hearing loss excitotoxicity 蝸電図内有毛細胞の変性遅発性神経細胞障害低体温内耳虚

项目摘要

Glutamate is a neurotransmitter at the synapse of the primary afferent auditory neuron. When the inner ear is damaged, it is released excessively to the surroundings and aggravates hearing loss by working toxic to them. In the first experiment, we investigated the mechanisms of hearing loss due to transient cochlear ischemia in gerbils. The results showed that cochlear ischemia for 5 min causes delayed neuronal death of the inner hair cells probably due to excitotoxicity of glutamate. This was supported by remarkable increase of glutamate concentration in the perilymph. In the second experiment, effects of hypothermia were investigated in gerbils with cochlear ischemia for 15 min. Hypothermia was very effective to prevent hearing loss due to cochlear anoxia. Loss of the hair cells in hyopthermic group was very few compared to those in normothermic group. In the third experiment, role of glutamate in noise induced hearing loss was studied in mouse which genetically lacks GLAST, a glutamate transporter. In GLAST lacking mouse, hearing loss due to continuous exposure to loud noise was greater than that in wild mouse. As GLAST resorbs glutamate in the synaptic space, metabolism of glutamate in the synapse of the primary afferent auditory neuron is important to prevent hearing loss by noise.

谷氨酸是初级传入听觉神经元突触的神经递质。当内耳受损时，它会过度释放到周围环境中，并通过对内耳产生毒性而加剧听力损失。在第一个实验中，我们研究了沙鼠短暂性耳蜗缺血导致听力损失的机制。结果表明，耳蜗缺血5分钟会导致内毛细胞延迟性神经元死亡，这可能是由于谷氨酸的兴奋性毒性所致。外淋巴中谷氨酸浓度的显着增加证实了这一点。在第二个实验中，研究了低温对耳蜗缺血 15 分钟的沙鼠的影响。低温对于预防耳蜗缺氧引起的听力损失非常有效。与常温组相比，低温组的毛细胞损失很少。在第三个实验中，在基因缺乏 GLAST（一种谷氨酸转运蛋白）的小鼠中研究了谷氨酸在噪声引起的听力损失中的作用。在缺乏GLAST的小鼠中，由于持续暴露于大声噪音而导致的听力损失比野生小鼠更大。由于 GLAST 在突触间隙中吸收谷氨酸，初级传入听觉神经元突触中谷氨酸的代谢对于防止噪音引起的听力损失非常重要。