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线粒体ATP合成酶8单核酸多态性影响氧化应激和小鼠的生存

Gesine Reichart¹, Johannes Mayer^2,3, Tursonjan Tokay^2,4

¹Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, Rostock, Germany. gesine.reichart@uni-rostock.de.

Pflugers Archiv : European journal of physiology

|September 20, 2025

概括

在MT-ATP8中,线粒体DNA (mtDNA) 单核酸多态性对空间学习和氧化应激产生了轻微影响. 然而,这种多态性与小鼠的寿命延长有关,这可能是由于线粒化.

科学领域:

线粒体遗传学线粒体遗传学
神经科学是一个神经科学.
衰老的研究研究.

背景情况:

线粒体DNA (mtDNA) 中的单核酸多态 (SNP) 可以导致严重的疾病.
对于能源生产至关重要的ATP合成酶包括mtDNA编码的亚单元ATP6和ATP8.
研究MT-ATP8SNP对细胞功能和寿命的影响对于了解疾病和衰老至关重要.

研究的目的:

在临床前小鼠模型中,研究MT-ATP8 SNP (m.7778G>T) 对记忆功能和相关生理参数的影响.
为了比较认知功能,氧化应激,神经元标记物和在MT-ATP8.8.中具有不同mtDNA序列的共塑性小鼠菌株之间的寿命.

主要方法:

使用了两个共塑性小鼠菌株:C57BL/6J-mtAKR/J (控制) 和C57BL/6J-mtFVB/NJ (携带m.7778G>T转变).
评估反应性氧物种 (ROS) 水平,空间学习 (莫里斯水迷宫) 和年轻 (3 个月) 和老年 (24 个月) 小鼠的长期增强.
通过免疫组织学量化NeuN和GFAP表达,并对两种菌株记录了寿命.

主要成果:

年龄较大的小鼠呈现出较高的海马ROS水平. 在MT-ATP8 SNP菌株和老年对照小鼠中,neuN/GFAP水平下降.
虽然老年小鼠在空间学习任务中表现较差,但没有观察到明显的菌株差异. 具有MT-ATP8 SNP的年轻小鼠显示突触可塑性降低.
与对照组相比,具有MT-ATP8 SNP的小鼠表现出延长寿命.

结论:

一个特定的MT-ATP8 SNP对空间学习和氧化应激的影响有限,因神经元组织而异.
在具有MT-ATP8 SNP的小鼠中观察到的延长寿命可能与线粒激进的概念有关.
这些发现有助于理解线粒体遗传学,衰老和寿命之间的复杂关系.

关键词:

这是ATP合成酶.年龄化衰老衰老认知认知是一种认知.混凝土塑料老鼠菌株的使用.寿命寿命寿命寿命寿命长期增强潜力长期增强潜力 MT-ATP8 在线学习 MtDNA变体的变体氧化应激是一种氧化应激.单核酸多态性的一种多态性.

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