Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Neuron. 2012 May 24;74(4):719-30. doi: 10.1016/j.neuron.2012.03.032.
Neuronal excitation can be substantially modulated by alterations in metabolism, as evident from the anticonvulsant effect of diets that reduce glucose utilization and promote ketone body metabolism. We provide genetic evidence that BAD, a protein with dual functions in apoptosis and glucose metabolism, imparts reciprocal effects on metabolism of glucose and ketone bodies in brain cells. These effects involve phosphoregulation of BAD and are independent of its apoptotic function. BAD modifications that reduce glucose metabolism produce a marked increase in the activity of metabolically sensitive K(ATP) channels in neurons, as well as resistance to behavioral and electrographic seizures in vivo. Seizure resistance is reversed by genetic ablation of the K(ATP) channel, implicating the BAD-K(ATP) axis in metabolic control of neuronal excitation and seizure responses.
神经元的兴奋可以通过代谢的改变来进行大幅度的调节，这一点从降低葡萄糖利用率和促进酮体代谢的饮食的抗惊厥作用中就可以明显看出。我们提供了遗传证据，表明 BAD 是一种在细胞凋亡和葡萄糖代谢中具有双重功能的蛋白质，它对脑细胞中葡萄糖和酮体代谢的相互作用有影响。这些影响涉及 BAD 的磷酸化调节，并且独立于其凋亡功能。降低葡萄糖代谢的 BAD 修饰会使神经元中代谢敏感的 K(ATP)通道的活性显著增加，同时也会使体内的行为和脑电图发作的易感性降低。通过基因敲除 K(ATP)通道，可逆转发作的抗性，这表明 BAD-K(ATP)轴在神经元兴奋和发作反应的代谢控制中具有重要作用。
