Pellerin Luc
Département de Physiologie, Université de Lausanne, Lausanne, Switzerland.
Curr Opin Clin Nutr Metab Care. 2008 Nov;11(6):701-5. doi: 10.1097/MCO.0b013e328312c368.
Almost 15 years after its initial proposal, the astrocyte-neuron lactate shuttle hypothesis still occupies the center stage in research on brain energetics. Recent developments have provided further evidence for its validity and have extended its application to different areas of neuroscience.
Description of cell-specific metabolic characteristics have reinforced the view that a prominent conversion of glucose into lactate takes place in astrocytes, whereas neurons preferentially take up and oxidize lactate over glucose-derived pyruvate. Indeed, specific mechanisms are activated by glutamatergic activity to favor such a net lactate transfer between the two cell types. Moreover, demonstration in vivo of the existence and implication of the astrocyte-neuron lactate shuttle hypothesis for particular neurophysiological processes is beginning to appear.
Brain energetics has undertaken its revolution. A new concept based on metabolic compartmentalization between astrocytes and neurons is establishing itself as the leading paradigm that opens new perspectives in areas such as functional brain imaging and regulation of energy homeostasis.
在最初提出近15年后,星形胶质细胞-神经元乳酸穿梭假说在脑能量代谢研究中仍占据核心地位。近期的进展为其有效性提供了进一步证据,并将其应用扩展到神经科学的不同领域。
对细胞特异性代谢特征的描述强化了这样一种观点,即星形胶质细胞中葡萄糖向乳酸的显著转化发生,而神经元优先摄取并氧化乳酸而非葡萄糖衍生的丙酮酸。事实上,谷氨酸能活性激活了特定机制,以促进两种细胞类型之间的这种净乳酸转移。此外,星形胶质细胞-神经元乳酸穿梭假说在特定神经生理过程中的存在及意义的体内证据也开始出现。
脑能量代谢已发生变革。基于星形胶质细胞和神经元之间代谢区室化的新概念正确立为主要范式,为功能性脑成像和能量稳态调节等领域开辟了新视角。