Administration of amitriptyline attenuates noise-induced hearing loss via glial cell line-derived neurotrophic factor (GDNF) induction
Administration of amitriptyline attenuates noise-induced hearing loss via glial cell line-derived neurotrophic factor (GDNF) induction
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DOI：
10.1016/j.brainres.2007.01.090
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发表时间：
2007-05-04
期刊：
影响因子：
2.9
通讯作者：
Yamashita, Toshio
中科院分区：
文献类型：
--
作者：
Shibata, Seiji Bruce;Osumi, Yasunori;Yamashita, Toshio
抗抑郁治疗已被描述为诱导神经营养因子（NTF）和逆转啮齿动物应激模型中观察到的细胞损失。阿米替林（Amitriptyline，AT）是一种三环类抗抑郁药，在最近的研究中被报道可诱导大鼠C6胶质母细胞瘤细胞合成和释放胶质细胞源性神经营养因子（glial cell line-derived neurotrophic factor，GDNF）。GDNF在以前的研究中已经显示出对声损伤的保护作用。因此，我们研究了AT是否可以诱导耳蜗GDNF的合成，减轻耳蜗对声损伤。我们使用Hartley豚鼠，腹膜内注射AT（30 mg/kg）或生理盐水。受试者暴露于中心频率为4 kHz的117 dB SPL倍频程噪声24 h。在注射前、噪声暴露后第3天和第7天，用4、8和16 kHz的听性脑干反应（ABR）评估噪声性听力损失（NIHL）。对于组织学评估，我们使用表面制备技术观察感觉上皮，并评估毛细胞（HC）损伤的定量。我们使用蛋白质印迹分析评估了AT给药后3、12和24小时，在有或没有强噪音暴露的情况下，耳蜗中GDNF的合成。在无噪声条件下，GDNF在注射后3 h和12 h均有表达，而在噪声条件下，GDNF的表达持续24 h。与生理盐水组相比，AT组ABR阈移明显降低，HC损伤明显减轻。这些结果表明，AT诱导的GDNF水平在耳蜗和衰减NIHL耳蜗损害的管理。(c)2007 Elsevier B. V.保留所有权利。
Antidepressant treatments have been described to induce neurotrophic factors (NTFs) and reverse the cell loss observed in rodent stress models. Amitriptyline (AT), a tricyclic antidepressant agent, has been reported in recent studies to induce glial cell line-derived neurotrophic factor (GDNF) synthesis and release in rat C6 glioblastoma cells. GDNF has shown protection against acoustic trauma in previous studies. Therefore, we investigated whether AT could induce GDNF synthesis in the cochlea and attenuate cochlea damage against acoustic trauma. We used Hartley guinea pigs and injected AT (30 mg/kg) or saline into the peritoneum. Subjects were exposed to 117 dB SPL octave band noise centered at 4 kHz for 24 h. Noise-induced hearing loss (NIHL) was assessed with auditory brain stem response (ABR) at 4, 8 and 16 kHz measured prior to the injection, 3 days and 7 days after noise exposure. For histological assessment, we observed the sensory epithelium using a surface preparation technique and assessed the quantitative hair cell (HC) damage. We evaluated GDNF synthesis with or without intense noise exposure at 3, 12 and 24 h after the administration of AT in the cochlea using Western blot analysis. GDNF expression was shown 3 h and 12 h after the injection without noise, whereas with noise the GDNF expression lasted for 24 h. The AT-administrated group showed significantly reduced ABR threshold shift and less HC damage than the saline-administrated group. These findings suggest that the administration of AT-induced GDNF levels in the cochlea and attenuated cochlea damage from NIHL. (c) 2007 Elsevier B.V. All rights reserved.