Is L-lactate a novel signaling molecule in the brain?
Is L-lactate a novel signaling molecule in the brain?
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DOI：
10.1038/jcbfm.2015.77
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发表时间：
2015-07
期刊：
影响因子：
--
通讯作者：
Kasparov S
中科院分区：
文献类型：
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作者：
Mosienko V;Teschemacher AG;Kasparov S
在大脑中，L-乳酸由神经元和星形胶质细胞产生。毫无疑问，神经元使用 L-乳酸作为补充燃料，尽管这种能量来源的重要性存在争议。无论其热量值如何，L-乳酸也可能在大脑中发挥信号作用。在这里，我们回顾了 L-乳酸介导的信号传导的几种当前假设。一些提出的机制需要 L-乳酸进入神经元，导致 ATP/ADP 比率或氧化还原状态发生变化。其他人则假设与已知受体 HCA1 (GPR81) 或新型尚未识别的受体相互作用。我们认为任何此类机制的敏感性都必须与细胞外 L-乳酸的浓度范围相匹配，在生理条件下该浓度范围小于约 1.5mmol/L。从这个角度来看，一些提出的机制需要 L-乳酸的超生理水平，并且当 L-乳酸浓度急剧上升时，可能会在缺血或癫痫发作期间发挥作用。目前，我们不知道大脑中 L-乳酸的产生是否发生在微域中，这可能会产生高于平均水平的局部浓度。尽管如此，很明显，在大脑中，就像在周围组织中一样，L-乳酸不仅用作能量来源，而且还充当信号分子。
In the brain, L-lactate is produced by both neurons and astrocytes. There is no doubt that neurons use L-lactate as a supplementary fuel although the importance of this energy source is disputed. Irrespective of its caloric value, L-lactate might also have a signaling role in the brain. Here, we review several current hypotheses of L-lactate mediated signaling. Some proposed mechanisms require L-lactate entry into the neurons leading to a shift in ATP/ADP ratio or redox state. Others postulate interaction with either known receptor HCA1 (GPR81) or a novel, yet unidentified receptor. We argue that the sensitivity of any such mechanism has to match the concentration range of extracellular L-lactate, which is less than ~1.5 mmol/L under physiologic conditions. From that point of view, some of the proposed mechanisms require supraphysiologic levels of L-lactate and could be engaged during ischemia or seizures when L-lactate concentration rises dramatically. Currently, we do not know whether L-lactate production in the brain occurs in microdomains, which might create higher than average local concentrations. Nevertheless, it is clear that in the brain, as in the peripheral tissues, L-lactate is not only used as a source of energy but also acts as a signaling molecule.