In Vivo Evidence for a Lactate Gradient from Astrocytes to Neurons
In Vivo Evidence for a Lactate Gradient from Astrocytes to Neurons
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DOI：
10.1016/j.cmet.2015.10.010
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发表时间：
2016-01-12
期刊：
影响因子：
29
通讯作者：
Weber, Bruno
中科院分区：
文献类型：
--
作者：
Machler, Philipp;Wyss, Matthias T.;Weber, Bruno
研究脑组织中的乳酸动力学具有挑战性，部分原因是无法获得细胞分辨率的体内数据。我们使用基因编码的FRET传感器Laconic结合双光子显微镜监测小鼠皮质星形胶质细胞和神经元中的乳酸。静脉内乳酸盐注射迅速增加星形胶质细胞和神经元中的Laconic信号，证明了跨组织的高乳酸盐渗透性。星形胶质细胞中的信号增加明显较小，这表明这些细胞中的基础乳酸水平较高，这一点通过一点校准方案得到证实。反式加速的单羧酸转运蛋白与丙酮酸能够减少细胞内的乳酸在星形胶质细胞，但不是在神经元。总的来说，这些数据提供了从星形胶质细胞到神经元的乳酸梯度的体内证据。该梯度是载体介导的乳酸从星形胶质细胞流向神经元的先决条件，因此支持星形胶质细胞-神经元乳酸穿梭模型，其中星形胶质细胞衍生的乳酸充当神经元的能量底物。
Investigating lactate dynamics in brain tissue is challenging, partly because in vivo data at cellular resolution are not available. We monitored lactate in cortical astrocytes and neurons of mice using the genetically encoded FRET sensor Laconic in combination with two-photon microscopy. An intravenous lactate injection rapidly increased the Laconic signal in both astrocytes and neurons, demonstrating high lactate permeability across tissue. The signal increase was significantly smaller in astrocytes, pointing to higher basal lactate levels in these cells, confirmed by a one-point calibration protocol. Trans-acceleration of the monocarboxylate transporter with pyruvate was able to reduce intracellular lactate in astrocytes but not in neurons. Collectively, these data provide in vivo evidence for a lactate gradient from astrocytes to neurons. This gradient is a prerequisite for a carrier-mediated lactate flux from astrocytes to neurons and thus supports the astrocyte-neuron lactate shuttle model, in which astrocyte-derived lactate acts as an energy substrate for neurons.