Rapamycin Added to Diet in Late Mid-Life Delays Age-Related Hearing Loss in UMHET4 Mice.
Rapamycin Added to Diet in Late Mid-Life Delays Age-Related Hearing Loss in UMHET4 Mice.
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DOI：
10.3389/fncel.2021.658972
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发表时间：
2021
影响因子：
5.3
通讯作者：
Dolan DF
中科院分区：
文献类型：
--
作者：
Altschuler RA;Kabara L;Martin C;Kanicki A;Stewart CE;Kohrman DC;Dolan DF
我们之前的研究表明，与没有雷帕霉素的小鼠相比，在4个月大时添加到饮食中的雷帕霉素在22个月大时耳蜗基底半部中与年龄相关的外毛细胞损失显著减少。目前的研究测试了在14个月大的时候在饮食中添加雷帕霉素，并增加了听觉脑干反应（ABR）的纵向评估。本研究使用UMHET 4小鼠，这是一种4向杂交，其中所有祖父母品系都缺乏易患早发性进行性听力损失的Cdh 23753 A等位基因。UMHET 4小鼠通常在16-17个月内具有正常听力，然后在低频/顶端耳蜗表现出阈值漂移，随后在更基底的高频区域表现出阈值漂移。在12、18和24月龄时评估4、12、24和48 kHz的ABR阈值，并与5月龄时获得的基线ABR阈值进行比较，以确定阈值偏移（TS）。在12月龄时，在任何检测频率下均未出现TS。在18月龄时，与对照饮食的小鼠相比，在14个月时将雷帕霉素添加到饮食中的小鼠在4和12 kHz下具有显著更低的平均TS，在24和48 kHz下没有显著差异。在24月龄时，雷帕霉素饮食组的平均4 kHz TS不再显著低于对照饮食组，而12 kHz平均值仍显著低于对照饮食组。在24个月时，雷帕霉素饮食组在24和48 kHz下的平均TS显著低于对照饮食组。在24个月时，大多数雷帕霉素和对照饮食小鼠耳蜗的顶半部分的毛细胞计数显示大量损失，组间无显著差异。在雷帕霉素组和对照组小鼠耳蜗的基底半部中仅存在轻度外毛细胞损失，组间无显著差异。结果表明，在小鼠模型中，晚年添加雷帕霉素可以降低与年龄相关的听力损失，然而，这也表明这种降低是延迟/减速，而不是完全预防。
Our previous study demonstrated rapamycin added to diet at 4 months of age had significantly less age-related outer hair cell loss in the basal half of the cochlea at 22 months of age compared to mice without rapamycin. The present study tested adding rapamycin to diet later in life, at 14 months of age, and added a longitudinal assessment of auditory brain stem response (ABR). The present study used UMHET4 mice, a 4 way cross in which all grandparental strains lack the Cdh23753A allele that predisposes to early onset, progressive hearing loss. UMHET4 mice typically have normal hearing until 16–17 months, then exhibit threshold shifts at low frequencies/apical cochlea and later in more basal high frequency regions. ABR thresholds at 4, 12, 24, and 48 kHz were assessed at 12, 18, and 24 months of age and compared to baseline ABR thresholds acquired at 5 months of age to determine threshold shifts (TS). There was no TS at 12 months of age at any frequency tested. At 18 months of age mice with rapamycin added to diet at 14 months had a significantly lower mean TS at 4 and 12 kHz compared to mice on control diet with no significant difference at 24 and 48 kHz. At 24 months of age, the mean 4 kHz TS in rapamycin diet group was no longer significantly lower than the control diet group, while the 12 kHz mean remained significantly lower. Mean TS at 24 and 48 kHz in the rapamycin diet group became significantly lower than in the control diet group at 24 months. Hair cell counts at 24 months showed large loss in the apical half of most rapamycin and control diet mice cochleae with no significant difference between groups. There was only mild outer hair cell loss in the basal half of rapamycin and control diet mice cochleae with no significant difference between groups. The results show that a later life addition of rapamycin can decrease age-related hearing loss in the mouse model, however, it also suggests that this decrease is a delay/deceleration rather than a complete prevention.
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影响因子：
7.8
作者：
Dai DF;Karunadharma PP;Chiao YA;Basisty N;Crispin D;Hsieh EJ;Chen T;Gu H;Djukovic D;Raftery D;Beyer RP;MacCoss MJ;Rabinovitch PS
通讯作者：
Rabinovitch PS
影响因子：
2.9
作者：
Ohlemiller, Kevin K.
通讯作者：
Ohlemiller, Kevin K.
影响因子：
2.4
作者：
Lin FR;Ferrucci L;Metter EJ;An Y;Zonderman AB;Resnick SM
通讯作者：
Resnick SM
影响因子：
7.8
作者：
Miller RA;Harrison DE;Astle CM;Fernandez E;Flurkey K;Han M;Javors MA;Li X;Nadon NL;Nelson JF;Pletcher S;Salmon AB;Sharp ZD;Van Roekel S;Winkleman L;Strong R
通讯作者：
Strong R
DOI：
10.1097/wnn.0b013e3181d748d7
发表时间：
2010-12
期刊：
Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology
影响因子：
--
作者：
Gates GA;Gibbons LE;McCurry SM;Crane PK;Feeney MP;Larson EB
通讯作者：
Larson EB