Huang Qiuhong, Ou Yongkang, Xiong Hao, Yang Haidi, Zhang Zhigang, Chen Suijun, Ye Yongyi, Zheng Yiqing
Department of Otolaryngology-HNS, Sun Yat-Sen Memorial Hospital and Institute of Hearing and Speech-Language Science, Sun Yat-Sen University, Guangzhou, China.
Audiol Neurootol. 2017;22(2):96-103. doi: 10.1159/000454874. Epub 2017 Aug 18.
The miR-34a/Bcl-2 signaling pathway may play a role in the mechanisms related to age-related hearing loss (AHL) in the auditory cortex.
The auditory cortex plays a key role in the recognition and processing of complex sound. It is difficult to explain why patients with AHL have poor speech recognition, so increasing numbers of studies have focused on its central change. Although micro (mi)RNAs in the central nervous system have recently been increasingly reported to be associated with age-related diseases, the molecular mechanisms of AHL in the auditory cortex are not fully understood.
The auditory brainstem response was used to assess the hearing ability of C57BL/6 mice, and q-PCR, immunohistochemistry, and Western blotting were used to detect the expression levels of miR-34a and Bcl-2 in the mouse auditory cortex. TUNEL and DNA fragmentation were adopted to detect the apoptosis of neurons in the auditory cortex. To verify the relationship of miR-34a and Bcl-2, we transfected an miR-34a mimic or miR-34a inhibitor into primary auditory cortex neurons.
In this study, miR-34a/Bcl-2 signaling was examined in auditory cortex neurons during aging. miR-34a and apoptosis increased in the auditory cortex neurons of C57BL/6 mice with aging, whereas an age-related decrease in Bcl-2 was determined. In the primary neurons of the auditory cortex, miR-34a overexpression inhibited Bcl-2, leading to an increase in apoptosis. Moreover, miR-34a knockdown increased Bcl-2 expression and diminished apoptosis.
Our results support a link between age-related apoptosis in auditory cortex neurons and miR-34a/Bcl-2 signaling, which may serve as a potential mechanism of the expression of AHL in the auditory cortex.
miR-34a/Bcl-2信号通路可能在与听觉皮层年龄相关性听力损失（AHL）相关的机制中发挥作用。
听觉皮层在复杂声音的识别和处理中起关键作用。很难解释为什么AHL患者的言语识别能力较差，因此越来越多的研究聚焦于其中枢变化。尽管最近越来越多的研究报道中枢神经系统中的微小（mi）RNA与年龄相关疾病有关，但AHL在听觉皮层中的分子机制尚未完全了解。
采用听觉脑干反应评估C57BL/6小鼠的听力，并用q-PCR、免疫组织化学和蛋白质印迹法检测小鼠听觉皮层中miR-34a和Bcl-2的表达水平。采用TUNEL和DNA片段化检测听觉皮层神经元的凋亡。为了验证miR-34a与Bcl-2的关系，我们将miR-34a模拟物或miR-34a抑制剂转染到原代听觉皮层神经元中。
在本研究中，对衰老过程中听觉皮层神经元中的miR-34a/Bcl-2信号进行了检测。随着年龄增长，C57BL/6小鼠听觉皮层神经元中的miR-34a和凋亡增加，而Bcl-2则呈现与年龄相关的下降。在听觉皮层的原代神经元中，miR-34a过表达抑制Bcl-2，导致凋亡增加。此外，miR-34a敲低增加了Bcl-2表达并减少了凋亡。
我们的结果支持听觉皮层神经元中与年龄相关的凋亡与miR-34a/Bcl-2信号之间的联系，这可能是听觉皮层中AHL表达的潜在机制。
