Department of Anesthesiology and Intensive Care, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.
Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.
Int J Mol Sci. 2024 Sep 6;25(17):9640. doi: 10.3390/ijms25179640.
Epilepsy is characterized by hypersynchronous neuronal discharges, which are associated with an increased cerebral metabolic rate of oxygen and ATP demand. Uncontrolled seizure activity (status epilepticus) results in mitochondrial exhaustion and ATP depletion, which potentially generate energy mismatch and neuronal loss. Many cells can adapt to increased energy demand by increasing metabolic capacities. However, acute metabolic adaptation during epileptic activity and its relationship to chronic epilepsy remains poorly understood. We elicited seizure-like events (SLEs) in an in vitro model of status epilepticus for eight hours. Electrophysiological recording and tissue oxygen partial pressure recordings were performed. After eight hours of ongoing SLEs, we used proteomics-based kinetic modeling to evaluate changes in metabolic capacities. We compared our findings regarding acute metabolic adaptation to published proteomic and transcriptomic data from chronic epilepsy patients. Epileptic tissue acutely responded to uninterrupted SLEs by upregulating ATP production capacity. This was achieved by a coordinated increase in the abundance of proteins from the respiratory chain and oxidative phosphorylation system. In contrast, chronic epileptic tissue shows a 25-40% decrease in ATP production capacity. In summary, our study reveals that epilepsy leads to dynamic metabolic changes. Acute epileptic activity boosts ATP production, while chronic epilepsy reduces it significantly.
癫痫的特征是神经元过度同步放电，这与大脑氧代谢率和 ATP 需求增加有关。不受控制的癫痫发作（癫痫持续状态）会导致线粒体衰竭和 ATP 耗竭，这可能会产生能量不匹配和神经元丢失。许多细胞可以通过增加代谢能力来适应能量需求的增加。然而，癫痫活动期间的急性代谢适应及其与慢性癫痫的关系仍知之甚少。我们在癫痫持续状态的体外模型中诱发了类似癫痫发作的事件（SLEs）持续 8 小时。进行了电生理记录和组织氧分压记录。在持续 8 小时的 SLEs 后，我们使用基于蛋白质组学的动力学建模来评估代谢能力的变化。我们将急性代谢适应的发现与慢性癫痫患者的已发表蛋白质组学和转录组学数据进行了比较。癫痫组织通过上调 ATP 产生能力对不间断的 SLEs 做出了急性反应。这是通过呼吸链和氧化磷酸化系统的蛋白质丰度的协调增加来实现的。相比之下，慢性癫痫组织的 ATP 产生能力下降了 25-40%。总之，我们的研究表明，癫痫会导致动态代谢变化。急性癫痫活动会促进 ATP 的产生，而慢性癫痫则会显著降低其产生。
