Monitoring ATP dynamics in electrically active white matter tracts
Monitoring ATP dynamics in electrically active white matter tracts
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DOI：
10.7554/elife.24241
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发表时间：
2017-04
期刊：
影响因子：
7.7
通讯作者：
Andrea Trevisiol;Aiman S. Saab;U. Winkler;Grit Marx;H. Imamura;W. Möbius;Kathrin Kusch;K. Nave;J. Hirrlinger
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文献类型：
--
作者：
Andrea Trevisiol;Aiman S. Saab;U. Winkler;Grit Marx;H. Imamura;W. Möbius;Kathrin Kusch;K. Nave;J. Hirrlinger
在几种神经退行性疾病和髓鞘疾病中，有髓鞘轴突的变性特征与潜在的能量缺乏是相容的。然而，目前不可能在电活性神经系统中选择性地测量轴突ATP水平。我们结合了转基因表达的ATP传感器在小鼠神经元与共聚焦FRET成像和电生理记录急性孤立的视神经。这使我们能够监测动态变化和活性依赖性轴突ATP稳态在细胞水平和真实的时间。我们发现ATP水平的变化与复合动作电位密切相关。然而，当乳酸代谢被抑制时，这种相关性被破坏，这表明轴突糖酵解产物不足以维持电活性轴突的线粒体能量代谢。细胞ATP和电活动的联合监测是研究正常生理和神经退行性疾病模型中神经元和胶质细胞能量代谢的新工具。DOI：http://dx.doi.org/10.7554/eLife.24241.001网站
In several neurodegenerative diseases and myelin disorders, the degeneration profiles of myelinated axons are compatible with underlying energy deficits. However, it is presently impossible to measure selectively axonal ATP levels in the electrically active nervous system. We combined transgenic expression of an ATP-sensor in neurons of mice with confocal FRET imaging and electrophysiological recordings of acutely isolated optic nerves. This allowed us to monitor dynamic changes and activity-dependent axonal ATP homeostasis at the cellular level and in real time. We find that changes in ATP levels correlate well with compound action potentials. However, this correlation is disrupted when metabolism of lactate is inhibited, suggesting that axonal glycolysis products are not sufficient to maintain mitochondrial energy metabolism of electrically active axons. The combined monitoring of cellular ATP and electrical activity is a novel tool to study neuronal and glial energy metabolism in normal physiology and in models of neurodegenerative disorders. DOI: http://dx.doi.org/10.7554/eLife.24241.001