Department of Otolaryngology-Head and Neck Surgery, University of California San Diego Health, 92037, La Jolla, CA, USA.
Cellular Neurobiology Laboratory, Salk Institute for Biological Studies, 92037, La Jolla, CA, USA.
J Mol Neurosci. 2023 May;73(4-5):307-315. doi: 10.1007/s12031-023-02119-w. Epub 2023 Apr 25.
In the senescence-accelerated mouse prone 8 (SAMP8) mouse model, oxidative stress leads to premature senescence and age-related hearing impairment (ARHI). CMS121 inhibits oxytosis/ferroptosis by targeting fatty acid synthase. The aim of our study was to determine whether CMS121 is protective against ARHI in SAMP8 mice. Auditory brainstem responses (ABRs) were used to assess baseline hearing in sixteen 4-week-old female SAMP8 mice, which were divided into two cohorts. The control group was fed a vehicle diet, while the experimental group was fed a diet containing CMS121. ABRs were measured until 13 weeks of age. Cochlear immunohistochemistry was performed to analyze the number of paired ribbon-receptor synapses per inner hair cell (IHC). Descriptive statistics are provided with mean ± SEM. Two-sample t-tests were performed to compare hearing thresholds and paired synapse count across the two groups, with alpha = 0.05. Baseline hearing thresholds in the control group were statistically similar to those of the CMS121 group. At 13 weeks of age, the control group had significantly worse hearing thresholds at 12 kHz (56.5 vs. 39.8, p = 0.044) and 16 kHz (64.8 vs. 43.8, p = 0.040) compared to the CMS121 group. Immunohistochemistry showed a significantly lower synapse count per IHC in the control group (15.7) compared to the CMS121 group (18.4), p = 0.014. Our study shows a significant reduction in ABR threshold shifts and increased preservation of IHC ribbon synapses in the mid-range frequencies among mice treated with CMS121 compared to untreated mice.
在快速老化品系 8 型（SAMP8）小鼠模型中，氧化应激导致早衰和与年龄相关的听力障碍（ARHI）。CMS121 通过靶向脂肪酸合酶抑制氧化应激/铁死亡。本研究旨在确定 CMS121 是否对 SAMP8 小鼠的 ARHI 具有保护作用。听觉脑干反应（ABR）用于评估 16 只 4 周龄雌性 SAMP8 小鼠的基线听力，这些小鼠分为两组。对照组喂食载体饮食，实验组喂食含有 CMS121 的饮食。ABR 测量一直持续到 13 周龄。进行耳蜗免疫组织化学分析以分析每个内毛细胞（IHC）的配对带受体突触数。提供描述性统计数据，平均值 ± SEM。使用双样本 t 检验比较两组之间的听力阈值和配对突触数，alpha 值 = 0.05。对照组的基线听力阈值与 CMS121 组的听力阈值统计学上相似。在 13 周龄时，与 CMS121 组相比，对照组在 12 kHz（56.5 与 39.8，p = 0.044）和 16 kHz（64.8 与 43.8，p = 0.040）的听力阈值明显更差。免疫组织化学显示，对照组每个 IHC 的突触数明显低于 CMS121 组（15.7 与 18.4，p = 0.014）。与未治疗的小鼠相比，用 CMS121 治疗的小鼠的 ABR 阈值变化明显减少，中频段 IHC 带突触的保存增加。
