Mitochondrial DNA 3,860-bp Deletion Increases with Aging in the Auditory Nervous System of C57BL/6J Mice
Mitochondrial DNA 3,860-bp Deletion Increases with Aging in the Auditory Nervous System of C57BL/6J Mice
复制标题
C57BL/6J 小鼠听觉神经系统中线粒体 DNA 3,860-bp 缺失随着衰老而增加
DOI：
10.1159/000499475
复制
发表时间：
2019-01-01
影响因子：
1.3
通讯作者：
Gong, Shusheng
中科院分区：
文献类型：
--
作者：
Du, Zheng-De;He, Lu;Gong, Shusheng
背景/目的：线粒体DNA （mtDNA）在衰老过程中对氧化损伤非常敏感，氧化损伤可导致mtDNA突变。先前的一项研究报道，3860 bp的mtDNA缺失，类似于人类4977 bp的mtDNA缺失，在小鼠组织中也很常见，并且随着年龄的增长在大脑和肝脏中增加。然而，以前没有研究评估这两个主题在小鼠听觉神经系统。方法：比较2、12、18月龄C57BL/6J小鼠外周（螺旋神经节，SG）和中枢（听觉皮层，AC）听觉神经系统mtDNA氧化损伤、线粒体超微结构变化和3860 bp缺失频率。结果：我们发现，随着年龄的增长，听觉脑干反应阈值随着8-羟基-2′-脱氧鸟苷（DNA氧化损伤标志物）在SG和AC神经元线粒体中的信号升高而升高。随着年龄的增长，SG和AC神经元的线粒体超微结构损伤也增加。此外，与2个月大的小鼠相比，SG组和AC组12月龄和18月龄小鼠中mtDNA 3860 -bp的相对缺失量显著高于AC组。结论：这些结果表明，mtDNA 3860 -bp缺失在小鼠听觉神经系统中很常见，并且随着年龄的增长而增加，可能导致与年龄相关的听力损失。
Background/Aims: Mitochondrial DNA (mtDNA) is sensitive to oxidative damage during aging, which can result in mtDNA mutations. A previous study reported that a 3,860-bp mtDNA deletion, similar to a 4,977-bp mtDNA deletion in humans, is also common occurrence in murine tissues, and increases in the brain and liver with aging. However, no previous study evaluated both topics in the murine auditory nervous system. Methods: We compared mtDNA oxidative damage, mitochondrial ultrastructural changes, and the frequency of the 3,860-bp deletion in the peripheral (spiral ganglion, SG) and central (auditory cortex, AC) auditory nervous system of C57BL/6J mice aged 2, 12, and 18 months. Results: We found that the threshold of auditory brainstem response increased with age along with the signal of 8-hydroxy-2′-deoxyguanosine – a marker of DNA oxidative damage – in the mitochondria of SG and AC neurons. The mitochondrial ultrastructural damage also increased with aging in the SG and AC neurons. Moreover, the relative amount of mtDNA 3,860-bp deletion in 12- and 18-month-old mice was significantly higher in the SG and AC as compared to 2-month-old mice. Conclusion: These results suggest that the mtDNA 3,860-bp deletion is common in the auditory nervous system of mice and increases with age and may contribute to age-related hearing loss.