AMP-Activated Protein Kinase Is Essential for the Maintenance of Energy Levels during Synaptic Activation

作者：Claudia Marinangeli, Sébastien Didier, Tariq Ahmed, Raphaëlle Caillerez, Manon Domise, Charlotte Laloux, Séverine Bégard, Sébastien Carrier, Morvane Colin, Philippe Marchetti, Bart Ghesquière, Detlef Balschun, Luc Buée, Jérôme Kluza, Valérie Vingtdeux · 发表于：iScience · 年份：2018 · DOI：10.1016/j.isci.2018.10.006 · 被引用次数：89 · 研究领域：Metabolism, Diabetes, and Cancer、Pancreatic function and diabetes、Mitochondrial Function and Pathology

Although the brain accounts for only 2% of the total body mass, it consumes the most energy. Neuronal metabolism is tightly controlled, but it remains poorly understood how neurons meet their energy demands to sustain synaptic transmission. Here we provide evidence that AMP-activated protein kinase (AMPK) is pivotal to sustain neuronal energy levels upon synaptic activation by adapting the rate of glycolysis and mitochondrial respiration. Furthermore, this metabolic plasticity is required for the expression of immediate-early genes, synaptic plasticity, and memory formation. Important in this context, in neurodegenerative disorders such as Alzheimer disease, dysregulation of AMPK impairs the metabolic response to synaptic activation and processes that are central to neuronal plasticity. Altogether, our data provide proof of concept that AMPK is an essential player in the regulation of neuroenergetic metabolic plasticity induced in response to synaptic activation and that its deregulation might lead to cognitive impairments.