Su Yu-Ting, Meng Xing-Xing, Zhang Xi, Guo Yi-Bin, Zhang Hai-Jun, Cheng Yao-Ping, Xie Xiao-Ping, Chang Yao-Ming, Bao Jun-Xiang
Department of Aerospace Hygiene, Fourth Military Medical University, Xi'an 710032, People's Republic of China.
Anat Rec (Hoboken). 2017 Dec;300(12):2220-2232. doi: 10.1002/ar.23677. Epub 2017 Aug 28.
Neuronal damage in primary auditory cortex (A1) underlies complex manifestations of noise exposure, prevention of which is critical for health maintenance. Acid sphingomyelinase (ASM) catalyzes generation of ceramide (Cer) which if over-activated mediates neuronal disorders in various diseases. Tricyclic antidepressants (TCAs), by restraining ASM/Cer, benefits multiple neuronal anomalies, so we aimed to elucidate the effect of TCA on noise induced hearing loss and auditory cortex derangement, unraveling mechanism involved. The mice were exposed to noise with frequencies of 20-20 KHz and intensity of 95 dB. Doxepin hydrochloride (DOX), a kind of TCAs, was given intragastrically by 5 mg kg days . Morphology of neurons was examined using hematoxylin-eosin (HE) and Nissl staining. Apoptosis was assayed through transferase-mediated dUTP nick end labeling (TUNEL). The content of ASM, Cer or acid ceramidase (AC) was detected by western blot and immunohistochemistry analysis. We demonstrated intense, broad band noise caused upward shift of auditory brainstem response (ABR) threshold to sound over frequencies 4-32 KHz, with prominent morphologic changes and enhanced apoptosis in neurons of primary auditory cortex (A1) (P < 0.05). DOX partly restored noise-caused hearing loss alleviating morphologic changes or apoptosis remarkably (P < 0.05). Both ASM and Cer abundance were elevated significantly by noise which was reversed upon DOX treatment (P < 0.05), but neither noise nor DOX altered AC content. DOX had no influence on hearing, neuronal morphology or ASM/Cer in control mice. Our result suggests DOX palliates noise induced hearing loss and neuronal damage in auditory cortex by correcting over-activation of ASM/Cer without hampering intrinsic behavior of it. Anat Rec, 300:2220-2232, 2017. © 2017 Wiley Periodicals, Inc.
初级听觉皮层（A1）中的神经元损伤是噪声暴露复杂表现的基础，预防这种损伤对维持健康至关重要。酸性鞘磷脂酶（ASM）催化神经酰胺（Cer）的生成，如果过度激活，神经酰胺会在各种疾病中介导神经元紊乱。三环类抗抑郁药（TCA）通过抑制ASM/Cer，对多种神经元异常有益，因此我们旨在阐明TCA对噪声诱导的听力损失和听觉皮层紊乱的影响，并揭示其中涉及的机制。将小鼠暴露于频率为20 - 20 KHz、强度为95 dB的噪声中。盐酸多塞平（DOX）是一种三环类抗抑郁药，以5 mg/kg/天的剂量灌胃给药。使用苏木精 - 伊红（HE）和尼氏染色检查神经元形态。通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）测定细胞凋亡。通过蛋白质免疫印迹和免疫组织化学分析检测ASM、Cer或酸性神经酰胺酶（AC）的含量。我们发现强烈的宽带噪声导致听觉脑干反应（ABR）阈值在4 - 32 KHz频率范围内对声音的向上偏移，初级听觉皮层（A1）神经元出现明显的形态学变化和细胞凋亡增加（P < 0.05）。DOX部分恢复了噪声引起的听力损失，显著减轻了形态学变化或细胞凋亡（P < 0.05）。噪声使ASM和Cer的丰度显著升高，DOX处理后逆转（P < 0.05），但噪声和DOX均未改变AC含量。DOX对对照小鼠的听力、神经元形态或ASM/Cer没有影响。我们的结果表明，DOX通过纠正ASM/Cer的过度激活来减轻噪声诱导的听力损失和听觉皮层神经元损伤，而不会妨碍其内在行为。《解剖学记录》，300:2220 - 2232，2017年。© 2017威利期刊公司。
