Differential age-related changes in mitochondrial DNA repair activities in mouse brain regions.
Differential age-related changes in mitochondrial DNA repair activities in mouse brain regions.
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DOI：
10.1016/j.neurobiolaging.2008.07.004
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发表时间：
2010-06
影响因子：
4.2
通讯作者：
Stevnsner, Tinna
中科院分区：
文献类型：
--
作者：
Gredilla, Ricardo;Garm, Christian;Holm, Rikke;Bohr, Vilhelm A.;Stevnsner, Tinna
大脑衰老的特征是对神经元损失和功能下降的易感性增加，线粒体DNA（mtDNA）突变被认为在这些过程中起重要作用。由于线粒体DNA与线粒体自由基产生的主要位点接近，氧化应激是线粒体中DNA突变的主要来源。碱基切除修复（BER）途径去除mtDNA的氧化损伤，从而构成避免mtDNA突变积累的重要机制。大脑的复杂性意味着暴露和防御氧化应激在大脑区域之间存在差异，因此某些区域可能特别容易积累mtDNA损伤。在目前的研究中，我们调查了BER途径的效率，在整个小鼠寿命的线粒体从皮层和海马，在哺乳动物的认知，这是中央地区，并在老化和神经退行性疾病的严重影响。线粒体DNA修复活性随年龄的增长而发生区域特异性调节。在皮质线粒体中，DNA糖基化酶活性在中年达到峰值，随后在老年显著下降。然而，在动物的整个寿命期间，在海马线粒体中只观察到微小的变化。此外，DNA糖基化酶活性在海马比皮质线粒体低。线粒体AP核酸内切酶活性增加，在老年动物的两个脑区。我们的数据表明，一个重要的区域特定的调节线粒体BER在衰老过程中。
Aging in the brain is characterized by increased susceptibility to neuronal loss and functional decline, and mitochondrial DNA (mtDNA) mutations are thought to play an important role in these processes. Due to the proximity of mtDNA to the main sites of mitochondrial free radical generation, oxidative stress is a major source of DNA mutations in mitochondria. The base excision repair (BER) pathway removes oxidative lesions from mtDNA, thereby constituting an important mechanism to avoid accumulation of mtDNA mutations. The complexity of the brain implies that exposure and defence against oxidative stress varies among brain regions and hence some regions may be particularly prone to accumulation of mtDNA damages. In the current study we investigated the efficiency of the BER pathway throughout the murine lifespan in mitochondria from cortex and hippocampus, regions that are central in mammalian cognition, and which are severely affected during aging and in neurodegenerative diseases. A regional specific regulation of mitochondrial DNA repair activities was observed with aging. In cortical mitochondria, DNA glycosylase activities peaked at middle-age followed by a significant drop at old age. However, only minor changes were observed in hippocampal mitochondria during the whole lifespan of the animals. Furthermore, DNA glycosylase activities were lower in hippocampal than in cortical mitochondria. Mitochondrial AP endonuclease activity increased in old animals in both brain regions. Our data suggest an important regional specific regulation of mitochondrial BER during aging.
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影响因子：
4.8
作者：
Hu, JP;de Souza-Pinto, NC;Bohr, VA
通讯作者：
Bohr, VA
DOI：
10.1016/j.bbrc.2005.07.201
发表时间：
2005-10-21
影响因子：
3.1
作者：
El Mohsen, MMA;Iravani, MM;Jenner, P
通讯作者：
Jenner, P
DOI：
10.1111/j.1532-5415.1972.tb00787.x
发表时间：
1972-01-01
影响因子：
6.3
作者：
HARMAN, D
通讯作者：
HARMAN, D
影响因子：
4.8
作者：
Dou, H;Mitra, S;Hazra, TK
通讯作者：
Hazra, TK
影响因子：
4.8
作者：
Hazra, TK;Kow, YW;Izumi, T
通讯作者：
Izumi, T