Zheng-De Du1, Lu He1, Chunmei Tu2, Xiao-An Guo3, Shukui Yu1, Ke Liu1, Shusheng Gong4. 1. Department of Otorhinolaryngology, Beijing Friendship Hospital, Capital Medical University, Beijing, China. 2. Department of Otorhinolaryngology, First People's Hospital of Jinan, Jinan, China. 3. Department of Otorhinolaryngology, First Affiliated Hospital of China Medical University, Shenyang, China. 4. Department of Otorhinolaryngology, Beijing Friendship Hospital, Capital Medical University, Beijing, China, gongss1962@163.com.
Abstract
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.
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.