Glymphatic clearance controls state-dependent changes in brain lactate concentration
Glymphatic clearance controls state-dependent changes in brain lactate concentration
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DOI：
10.1177/0271678x16661202
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发表时间：
2017-06-01
影响因子：
6.3
通讯作者：
Nedergaard, Maiken
中科院分区：
文献类型：
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作者：
Lundgaard, Iben;Lu, Minh Lon;Nedergaard, Maiken
清醒时脑乳酸浓度高于睡眠时。然而，目前尚不清楚为什么觉醒与大脑乳酸增加有关，以及为什么乳酸在睡眠几分钟内下降。在这里，我们表明类淋巴系统负责大脑乳酸浓度的状态依赖性变化。通过乙酰唑胺治疗、小脑延髓池穿刺、水通道蛋白 4 缺失或体位改变来抑制类淋巴功能，可减少清醒小鼠进入睡眠或麻醉时通常观察到的脑乳酸下降。同时，当小鼠麻醉时，相同的操作减少了颈部乳酸的积累，但没有减少腹股沟淋巴结的乳酸积累。因此，我们的研究表明，脑乳酸是睡眠-觉醒周期的极佳生物标志物，并且在睡眠剥夺期间进一步增加，因为脑乳酸与类淋巴清除率呈负相关。该分析通过证明未完全氧化的葡萄糖可以通过类淋巴液运输以乳酸形式输出，为大脑能量代谢提供了基本的新见解。
Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lactate concentration. Suppression of glymphatic function via acetazolamide treatment, cisterna magna puncture, aquaporin 4 deletion, or changes in body position reduced the decline in brain lactate normally observed when awake mice transition into sleep or anesthesia. Concurrently, the same manipulations diminished accumulation of lactate in cervical, but not in inguinal lymph nodes when mice were anesthetized. Thus, our study suggests that brain lactate is an excellent biomarker of the sleep-wake cycle and increases further during sleep deprivation, because brain lactate is inversely correlated with glymphatic-lymphatic clearance. This analysis provides fundamental new insight into brain energy metabolism by demonstrating that glucose that is not fully oxidized can be exported as lactate via glymphatic-lymphatic fluid transport.