Age-Dependent Up-Regulation of HCN Channels in Spiral Ganglion Neurons Coincide With Hearing Loss in Mice.
Age-Dependent Up-Regulation of HCN Channels in Spiral Ganglion Neurons Coincide With Hearing Loss in Mice.
复制标题
螺旋神经节神经元中 HCN 通道的年龄依赖性上调与小鼠听力损失同时发生。
DOI：
10.3389/fnagi.2018.00353
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发表时间：
2018
影响因子：
4.8
通讯作者：
Lv P
中科院分区：
文献类型：
--
作者：
Shen H;Liu W;Geng Q;Li H;Lu M;Liang P;Zhang B;Yamoah EN;Lv P
年龄相关性听力损失（AHL）是老年人最常见的感觉障碍，其病因多种多样。为了了解AHL的潜在机制，一种策略是确定疾病的相关因素，以便对治疗方法进行综合评估。螺旋神经节神经元（sgn）功能障碍和变性是AHL的主要原因。先前，我们发现听觉系统老化的变化之一是小鼠SGN兴奋性增加。由于超极化激活的环核苷酸门控（HCN）通道在决定神经元兴奋性中起重要作用，我们预测sgn中的HCN通道参与了AHL。为了研究HCN通道对AHL的贡献，我们检测了成年（2-3个月）和11 - 12个月大小鼠sgn中HCN通道的表达和生物物理特性。我们报道了老龄小鼠（11-12个月大）sgn中HCN通道电流（Ih）的急剧增加。结果与HCN1和HCN2亚基的表达增加相吻合，表明sgn中HCN通道的上调是sgn老化的重要方面之一。此外，Ih的活性对老年小鼠sgn的放电特性产生了重大影响。Ih的上调可能通过调节SGN的兴奋性来促进AHL。我们评估了sgn兴奋性增加是否与神经变性相吻合。在老年小鼠中观察到凋亡诱导因子（AIF）介导的sgn细胞凋亡，HCN通道的激活介导了AIF的激活。因此，这些研究结果表明，年龄依赖性HCN通道和Ih的表达增加与sgn细胞凋亡之间存在明显的相关性，这可能有助于AHL的多种机制。
Age-related hearing loss (AHL) is the most common sensory disorder in the elderly population, and the etiologies are diverse. To understand the underlying mechanisms of AHL, one strategy is to identify correlates of the disease for comprehensive evaluation of treatment approaches. Dysfunction and degeneration of spiral ganglion neurons (SGNs) are major contributors to AHL. Previously, we showed that one of the changes in the aging auditory system is SGN excitability increase in mice. Since hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play important roles in determining neuronal excitability, we predicted that HCN channels in SGNs are involved in AHL. To investigate the contribution of HCN channels to AHL, we examined the expression and biophysical properties of HCN channels in SGNs from adult (2–3 months) and 11–12-month-old mice. We report a dramatic increase of HCN channel current (Ih) in SGNs in old mice (11–12 months old). The results matched well with increased expression of HCN1 and HCN2 subunits, suggesting that upregulation of HCN channels in SGNs is one of the important facets of the aging SGNs. Moreover, the activity of Ih produced a major impact on the firing properties of SGNs in older mice. The upregulation of Ih may contribute to AHL by regulating SGN excitability. We assessed whether increased SGNs excitability dovetail with neurodegeneration. Apoptosis-inducing factor (AIF)-mediated apoptosis in SGNs was observed in old mice and activation of HCN channels mediates AIF activation. Thus, these findings demonstrate stark correlation between age-dependent increased expression of HCN channels and Ih, and apoptosis in SGNs, which may contribute towards the varied mechanisms of AHL.
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影响因子：
2.8
作者：
Schettino, Amy E.;Lauer, Amanda M.
通讯作者：
Lauer, Amanda M.
影响因子：
11.4
作者：
Norberg, Erik;Karlsson, Marie;Korenovska, Olga;Szydlowski, Susanne;Silberberg, Gilad;Uhlen, Per;Orrenius, Sten;Zhivotovsky, Boris
通讯作者：
Zhivotovsky, Boris
DOI：
10.18632/aging.101045
发表时间：
2016-09-23
期刊：
Aging
影响因子：
--
作者：
Frisina RD;Ding B;Zhu X;Walton JP
通讯作者：
Walton JP
影响因子：
2.8
作者：
Chen, C
通讯作者：
Chen, C
影响因子：
168.9
作者：
Gates, GA;Mills, JH
通讯作者：
Mills, JH