| Project/Area Number |
23390393
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
IWASAKI Shin-ichi 東京大学, 大学院・医学系研究科, 准教授 (10359606)
KIKKAWA Yayoi 東京大学, 医学部附属病院, 病院診療医 (00452350)
SAKAMOTO Takashi 東京大学, 大学院・医学系研究科, 講師 (50323548)
KASHIO Akinori 東京大学, 大学院・医学系研究科, 助教 (20451809)
YASUI Takuya 帝京大学, 医学部附属病院, 助教 (50511466)
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| Co-Investigator(Renkei-kenkyūsha) |
PROLLA Tomas A. ウィスコンシン大学, 医学部, 教授
SOMEYA Shin-ichi フロリダ大学, 老化研究所, 准教授 (50554490)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2013: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2012: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2011: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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| Keywords | .老化 / 蝸牛 / ミトコンドリア / 酸化ストレス / 老化 / 動物 / マイクロアレイ / 脳・神経 |
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| Research Abstract |
We investigated the association of oxidative stress and age-related hearing loss (AHL) using several transgenic mice in which the oxidative stress is enhanced or suppressed. We first examined whether reduction in manganese superoxide dismutase (Mn-SOD) accelerated AHL. At 16 months, immunoreactivity of 8-hydroxydeoxyguanosine was significantly greater in Mn-SOD heterozygous knockout (HET) mice compared to WT mice, but that of 4-hydroxynonenal did not differ between them. Age-related ABR threshold shifts and the extent of cochlear degeneration did not differ between WT and HET mice, suggesting that decrease of Mn-SOD by half increases oxidative stress in the cochlea to some extent but does not accelerate AHL. In contrast, glutathion reductase knockout mice exhibited acceleration of ABR threshold shifts at high frequencies, suggesting that oxidization of glutathione is crucial in the development of AHL.
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