Neuroscience Program, University of Illinois at Urbana-Champaign, Champaign, Illinois, United States of America.
PLoS One. 2011;6(12):e28427. doi: 10.1371/journal.pone.0028427. Epub 2011 Dec 13.
When administered either systemically or centrally, glucose is a potent enhancer of memory processes. Measures of glucose levels in extracellular fluid in the rat hippocampus during memory tests reveal that these levels are dynamic, decreasing in response to memory tasks and loads; exogenous glucose blocks these decreases and enhances memory. The present experiments test the hypothesis that glucose enhancement of memory is mediated by glycogen storage and then metabolism to lactate in astrocytes, which provide lactate to neurons as an energy substrate. Sensitive bioprobes were used to measure brain glucose and lactate levels in 1-sec samples. Extracellular glucose decreased and lactate increased while rats performed a spatial working memory task. Intrahippocampal infusions of lactate enhanced memory in this task. In addition, pharmacological inhibition of astrocytic glycogenolysis impaired memory and this impairment was reversed by administration of lactate or glucose, both of which can provide lactate to neurons in the absence of glycogenolysis. Pharmacological block of the monocarboxylate transporter responsible for lactate uptake into neurons also impaired memory and this impairment was not reversed by either glucose or lactate. These findings support the view that astrocytes regulate memory formation by controlling the provision of lactate to support neuronal functions.
当葡萄糖被系统或中枢给药时，它是记忆过程的有力增强剂。在大鼠海马体的记忆测试中，测量细胞外液中的葡萄糖水平，结果表明这些水平是动态的，会随着记忆任务和负荷的增加而降低；外源性葡萄糖可阻止这些降低并增强记忆。本实验检验了这样一个假设，即葡萄糖增强记忆是通过在星形胶质细胞中储存糖原并随后代谢为乳酸来介导的，星形胶质细胞将乳酸作为能量底物提供给神经元。使用灵敏的生物探针在 1 秒的样本中测量脑内的葡萄糖和乳酸水平。当大鼠执行空间工作记忆任务时，细胞外葡萄糖减少，乳酸增加。海马内注射乳酸可增强该任务中的记忆。此外，星形胶质细胞糖原分解的药理学抑制会损害记忆，而通过给予乳酸或葡萄糖可以逆转这种损害，这两者都可以在没有糖原分解的情况下为神经元提供乳酸。负责将乳酸摄取到神经元中的单羧酸转运蛋白的药理学阻断也会损害记忆，并且葡萄糖或乳酸都不能逆转这种损害。这些发现支持了这样一种观点，即星形胶质细胞通过控制为支持神经元功能提供乳酸来调节记忆形成。
