Huang Xinghua, Chen Mo, Ding Yan, Wang Qin
Department of Ultrasound Diagnosis, the Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, Hunan, 410011, China.
Department of Otolaryngology-Head and Neck Surgery, the Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, Hunan, 410011, China.
Genesis. 2017 Mar;55(3). doi: 10.1002/dvg.23016. Epub 2017 Feb 13.
Neuronal hearing loss has become a prevalent health problem. This study focused on the function of arctigenin (ARC) in promoting survival and neuronal differentiation of mouse cochlear neural stem cells (NSCs), and its protection against gentamicin (GMC) induced neuronal hearing loss. Mouse cochlea was used to isolate NSCs, which were subsequently cultured in vitro. The effects of ARC on NSC survival, neurosphere formation, differentiation of NSCs, neurite outgrowth, and neural excitability in neuronal network in vitro were examined. Mechanotransduction ability demonstrated by intact cochlea, auditory brainstem response (ABR), and distortion product optoacoustic emissions (DPOAE) amplitude in mice were measured to evaluate effects of ARC on GMC-induced neuronal hearing loss. ARC increased survival, neurosphere formation, neuron differentiation of NSCs in mouse cochlear in vitro. ARC also promoted the outgrowth of neurites, as well as neural excitability of the NSC-differentiated neuron culture. Additionally, ARC rescued mechanotransduction capacity, restored the threshold shifts of ABR and DPOAE in our GMC ototoxicity murine model. This study supports the potential therapeutic role of ARC in promoting both NSCs proliferation and differentiation in vitro to functional neurons, thus supporting its protective function in the therapeutic treatment of neuropathic hearing loss in vivo.
神经元性听力损失已成为一个普遍的健康问题。本研究聚焦于牛蒡子苷元（ARC）在促进小鼠耳蜗神经干细胞（NSCs）存活和神经元分化方面的作用，以及其对庆大霉素（GMC）诱导的神经元性听力损失的保护作用。使用小鼠耳蜗分离NSCs，随后在体外进行培养。检测了ARC对体外培养的NSCs存活、神经球形成、NSCs分化、神经突生长以及神经网络中神经兴奋性的影响。测量完整耳蜗所表现出的机械转导能力、小鼠的听觉脑干反应（ABR）和畸变产物耳声发射（DPOAE）幅度，以评估ARC对GMC诱导的神经元性听力损失的影响。ARC增加了体外培养的小鼠耳蜗NSCs的存活、神经球形成和神经元分化。ARC还促进了神经突的生长以及NSC分化的神经元培养物的神经兴奋性。此外，在我们的GMC耳毒性小鼠模型中，ARC挽救了机械转导能力，恢复了ABR和DPOAE的阈值变化。本研究支持了ARC在促进体外NSCs增殖和分化为功能性神经元方面的潜在治疗作用，从而支持了其在体内治疗神经性听力损失中的保护功能。
