Department of Physiology, Shantou University Medical College, Shantou, China.
CNS Neurosci Ther. 2012 Aug;18(8):641-6. doi: 10.1111/j.1755-5949.2012.00337.x. Epub 2012 May 22.
To evaluate the acute effects of the mitochondrial complex I inhibitor rotenone on rat hippocampal synaptic plasticity.
Electrophysiological field potential recordings were used to measure basal synaptic transmission and synaptic plasticity in rat coronal hippocampal slices. Synaptic long-term potentiation (LTP) was induced by high-frequency stimulation (100 Hz, 1 second × 3 at an interval of 20 seconds). In addition, mitochondrial complex I function was measured using MitoSOX imaging in mitochondrial preparations.
Acute exposure of hippocampal slices to 50 nM rotenone for 1 h did not alter basal CA3-CA1 synaptic transmission though 500 nM rotenone significantly reduced basal synaptic transmission. However, 50 nM rotenone significantly impaired LTP and this rotenone's effect was prevented by co-application of rotenone plus the ketones acetoacetate and β-hydroxybutyrate (1 mM each). Finally, we measured mitochondrial function using MitoSOX imaging in mitochondrial preparations and found that 50 nM rotenone partially reduced mitochondrial function whereas 500 nM rotenone completely eliminated mitochondrial function.
Our findings suggest that mitochondrial activity driven by complex I is a sensitive modulator of synaptic plasticity in the hippocampus. Acute exposure of the hippocampus to rotenone eliminates complex I function and in turn impairs LTP.
评估线粒体复合物 I 抑制剂鱼藤酮对大鼠海马突触可塑性的急性影响。
用电生理学场电位记录来测量大鼠冠状海马切片中的基础突触传递和突触可塑性。通过高频刺激（100 Hz，1 秒×3，间隔 20 秒）诱导突触长时程增强（LTP）。此外，还使用线粒体制备中的 MitoSOX 成像来测量线粒体复合物 I 功能。
海马切片急性暴露于 50 nM 鱼藤酮 1 小时不会改变基础 CA3-CA1 突触传递，但 500 nM 鱼藤酮显著降低了基础突触传递。然而，50 nM 鱼藤酮显著损害了 LTP，而鱼藤酮与酮体乙酰乙酸盐和β-羟基丁酸（各 1 mM）联合应用则可预防这种损害。最后，我们使用线粒体制备中的 MitoSOX 成像测量了线粒体功能，发现 50 nM 鱼藤酮部分降低了线粒体功能，而 500 nM 鱼藤酮则完全消除了线粒体功能。
我们的研究结果表明，由复合物 I 驱动的线粒体活性是海马突触可塑性的敏感调节剂。海马的急性暴露于鱼藤酮会消除复合物 I 的功能，进而损害 LTP。
