Cortada Maurizio, Levano Soledad, Bodmer Daniel
Department of Biomedicine, University of Basel, Basel, Switzerland.
Audiol Neurootol. 2017;22(3):125-134. doi: 10.1159/000479218. Epub 2017 Sep 9.
Brimonidine, an alpha-2 adrenergic receptor (α2-AR) agonist, has neuroprotective effects in the visual system and in spiral ganglion neurons. Auditory hair cells (HCs) express all 3 α2-AR subtypes, but their roles in HCs remain unknown. This study investigated the effects of brimonidine on auditory HCs that were also exposed to gentamicin, which is toxic to HCs. Organ of Corti explants were exposed to gentamicin in the presence or absence of brimonidine, and the α2-AR protein expression levels and Erk1/2 and Akt phosphorylation levels were determined. Brimonidine had a protective effect on auditory HCs against gentamicin-induced toxicity that was blocked by yohimbine. This suggested that the protective effect of brimonidine on HCs was mediated by the α2-AR. None of the treatments altered α2-AR protein expression levels, and brimonidine did not significantly change the activation levels of the Erk1/2 and Akt proteins. These observations indicated that brimonidine, acting directly via α2-AR, protects HCs from gentamicin-induced toxicity. Therefore, brimonidine shows potential for preventing or treating sensorineural hearing loss.
溴莫尼定是一种α2肾上腺素能受体(α2-AR)激动剂,在视觉系统和螺旋神经节神经元中具有神经保护作用。听觉毛细胞(HCs)表达所有三种α2-AR亚型,但其在毛细胞中的作用尚不清楚。本研究调查了溴莫尼定对同时暴露于对毛细胞有毒性的庆大霉素的听觉毛细胞的影响。在有或没有溴莫尼定的情况下,将柯蒂氏器外植体暴露于庆大霉素,并测定α2-AR蛋白表达水平以及Erk1/2和Akt的磷酸化水平。溴莫尼定对听觉毛细胞具有保护作用,可对抗庆大霉素诱导的毒性,而育亨宾可阻断这种保护作用。这表明溴莫尼定对毛细胞的保护作用是由α2-AR介导的。所有处理均未改变α2-AR蛋白表达水平,且溴莫尼定未显著改变Erk1/2和Akt蛋白的激活水平。这些观察结果表明,溴莫尼定通过α2-AR直接发挥作用,保护毛细胞免受庆大霉素诱导的毒性。因此,溴莫尼定在预防或治疗感音神经性听力损失方面具有潜力。