Ma Weiyuan, Berg Jim, Yellen Gary
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Neurosci. 2007 Apr 4;27(14):3618-25. doi: 10.1523/JNEUROSCI.0132-07.2007.
A low-carbohydrate ketogenic diet remains one of the most effective (but mysterious) treatments for severe pharmacoresistant epilepsy. We have tested for an acute effect of physiological ketone bodies on neuronal firing rates and excitability, to discover possible therapeutic mechanisms of the ketogenic diet. Physiological concentrations of ketone bodies (beta-hydroxybutyrate or acetoacetate) reduced the spontaneous firing rate of neurons in slices from rat or mouse substantia nigra pars reticulata. This region is thought to act as a "seizure gate," controlling seizure generalization. Consistent with an anticonvulsant role, the ketone body effect is larger for cells that fire more rapidly. The effect of ketone bodies was abolished by eliminating the metabolically sensitive K(ATP) channels pharmacologically or by gene knock-out. We propose that ketone bodies or glycolytic restriction treat epilepsy by augmenting a natural activity-limiting function served by K(ATP) channels in neurons.
低碳水化合物生酮饮食仍然是治疗严重药物抵抗性癫痫最有效的（但却神秘的）方法之一。我们测试了生理酮体对神经元放电频率和兴奋性的急性影响，以探寻生酮饮食可能的治疗机制。生理浓度的酮体（β-羟基丁酸或乙酰乙酸）降低了来自大鼠或小鼠黑质网状部切片中神经元的自发放电频率。该区域被认为起到“癫痫发作闸门”的作用，控制癫痫发作的扩散。与抗惊厥作用一致，酮体对放电更快的细胞的作用更大。通过药理学方法消除代谢敏感的K(ATP)通道或通过基因敲除，酮体的作用被消除。我们提出，酮体或糖酵解限制通过增强神经元中K(ATP)通道所发挥的天然活动限制功能来治疗癫痫。
