TRIMETHYLTIN EFFECTS ON AUDITORY FUNCTION AND COCHLEAR MORPHOLOGY
TRIMETHYLTIN EFFECTS ON AUDITORY FUNCTION AND COCHLEAR MORPHOLOGY
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DOI：
10.1016/0041-008x(90)90364-z
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发表时间：
1990-08-01
影响因子：
3.8
通讯作者：
JANSSEN, R
中科院分区：
文献类型：
--
作者：
CROFTON, KM;DEAN, KF;JANSSEN, R
三甲基锡（TMT）是一种已知能改变听觉功能的神经毒物。本研究旨在利用行为学、电生理学和解剖学技术来比较tmt诱发的听觉功能障碍。成年雄性Long-Evans连帽大鼠（n = 9-12/组）急性暴露于生理盐水、3、5或7 mg/kg TMT。使用听觉惊吓反应（ASR）的反射修饰，在给药后11周测定5 khz和40 khz音调的听觉阈值。在给药9周后测定5 khz、40 khz和80 khz音调刺激的脑干听觉诱发反应阈值。给药后13周评估耳蜗组织学。功能终点显示高频听力损失。在所有剂量组中，40 khz音调的ASR阈值均升高25-35 dB。在5和7 mg/kg组中，40和80 khz音调的BAER阈值升高了30-50 dB。Corti器官表面制剂显示出典型耳毒性损伤模式。也就是说，外毛细胞在与高频听力相关的区域以剂量依赖的方式从基部到顶点优先死亡。这些数据证明了ASR和BAER在检测听力功能改变方面的效用，并表明tmt引起的高频听力损失与耳蜗损伤有关。
Trimethyltin (TMT) is a neurotoxicant known to alter auditory function. The present study was designed to compare TMT-induced auditory dysfunction using behavioral, electrophysiological, and anatomical techniques. Adult male Long-Evans hooded rats (n = 9-12/group) were acutely exposed to saline, 3, 5, or 7 mg/kg TMT. Auditory thresholds were determined 11 weeks postdosing for 5- and 40-kHz tones using reflex modification of the auditory startle response (ASR). Brainstem auditory evoked response (BAER) thresholds were determined for 5-, 40- and 80-kHz tonal stimuli 9 weeks postdosing. Cochlear histology was assessed at 13 weeks postdosing. Functional endpoints demonstrated a high-frequency hearing loss. ASR thresholds for 40-kHz tones were elevated 25-35 dB in all dosage groups. BAER thresholds for 40- and 80-kHz tones were elevated 30-50 dB in the 5 and 7 mg/kg groups. Organ of Corti surface preparations revealed a pattern of damage suggesting classical ototoxicity. That is, outer hair cells died preferentially in regions associated with high-frequency hearing, in a dosage-dependent manner from base to apex. These data demonstrate the utility of the ASR and BAER in detecting functional alterations in audition and indicate that TMT-induced high-frequency hearing loss is associated with cochlear damage.