Marinangeli Claudia, Didier Sébastien, Ahmed Tariq, Caillerez Raphaelle, Domise Manon, Laloux Charlotte, Bégard Séverine, Carrier Sébastien, Colin Morvane, Marchetti Philippe, Ghesquière Bart, Balschun Detlef, Buée Luc, Kluza Jérôme, Vingtdeux Valérie
Univ. Lille, Inserm, CHU-Lille, UMR-S1172, Jean-Pierre Aubert Research Centre, Bâtiment Biserte, Place de Verdun, Lille 59045, France.
Brain & Cognition, Faculty of Psychology and Educational Sciences, KU Leuven, Leuven, Belgium; Leuven Research Institute for Neuroscience & Disease (LIND), KU Leuven, Leuven, Belgium; Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University, Doha, Qatar.
iScience. 2018 Nov 30;9:1-13. doi: 10.1016/j.isci.2018.10.006. Epub 2018 Oct 12.
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.
尽管大脑仅占全身质量的2%，但其消耗的能量却是最多的。神经元代谢受到严格调控，但对于神经元如何满足其能量需求以维持突触传递，我们仍知之甚少。在此，我们提供证据表明，AMP激活的蛋白激酶（AMPK）通过调节糖酵解速率和线粒体呼吸作用，在突触激活后维持神经元能量水平方面起着关键作用。此外，这种代谢可塑性对于即时早期基因的表达、突触可塑性和记忆形成是必需的。在此背景下重要的是，在诸如阿尔茨海默病等神经退行性疾病中，AMPK的失调会损害对突触激活的代谢反应以及对神经元可塑性至关重要的过程。总之，我们的数据提供了概念验证，即AMPK是调节突触激活诱导的神经能量代谢可塑性的关键参与者，其失调可能导致认知障碍。
