Ketones prevent synaptic dysfunction induced by mitochondrial respiratory complex inhibitors.
Ketones prevent synaptic dysfunction induced by mitochondrial respiratory complex inhibitors.
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DOI：
10.1111/j.1471-4159.2010.06728.x
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发表时间：
2010-07
影响因子：
4.7
通讯作者：
Rho JM
中科院分区：
文献类型：
--
作者：
Kim DY;Vallejo J;Rho JM
酮先前在神经退行性疾病模型中显示出有益作用，特别是针对相关的线粒体功能障碍和认知障碍。然而，酮的突触保护作用的证据仍然缺乏。我们使用电生理学、活性氧（ROS）成像和生化技术测试了酮对线粒体呼吸复合物（MRC）抑制剂诱导的突触损伤的影响。MRC抑制剂剂量依赖性地抑制CA 1海马中的群体尖峰（PS）和场电位振幅。酮的预处理强烈阻止PS的变化，而部分保护被认为是在场电位。鱼藤酮（Rot; 100 nmol/L），MRC I抑制剂，抑制突触功能，而不改变ROS水平和PS抑制由Rot不受抗氧化剂的影响。相反，抗氧化剂诱导的PS恢复对MRC II抑制剂3-硝基丙酸（3-NP; 1 mmol/L）是类似的酮的突触保护作用。酮也抑制3-NP诱导的ROS产生。最后，酮逆转了由Rot和3-NP引起的ATP水平下降。总之，我们的数据表明，酮可以保护突触功能在CA 1海马MRC功能障碍诱导，可能通过抗氧化作用和增强ATP的产生。
Ketones have previously shown beneficial effects in models of neurodegenerative disorders, particularly against associated mitochondrial dysfunction and cognitive impairment. However, evidence of a synaptic protective effect of ketones remains lacking. We tested the effects of ketones on synaptic impairment induced by mitochondrial respiratory complex (MRC) inhibitors using electrophysiological, reactive oxygen species (ROS) imaging and biochemical techniques. MRC inhibitors dose-dependently suppressed both population spike (PS) and field potential amplitudes in the CA1 hippocampus. Pre-treatment with ketones strongly prevented changes in the PS, whereas partial protection was seen in the field potential. Rotenone (Rot; 100 nmol/L), a MRC I inhibitor, suppressed synaptic function without altering ROS levels and PS depression by Rot was unaffected by antioxidants. In contrast, antioxidant-induced PS recovery against the MRC II inhibitor 3-nitropropionic acid (3-NP; 1 mmol/L) was similar to the synaptic protective effects of ketones. Ketones also suppressed ROS generation induced by 3-NP. Finally, ketones reversed the decreases in ATP levels caused by Rot and 3-NP. In summary, our data demonstrate that ketones can preserve synaptic function in CA1 hippocampus induced by MRC dysfunction, likely through an antioxidant action and enhanced ATP generation.
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影响因子：
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DOI：
10.1097/mco.0b013e3282f44c06
发表时间：
2008-03-01
影响因子：
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作者：
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通讯作者：
Rho, Jong M.