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首页> 外文期刊>Neuron >Metabolic Communication between Astrocytes and Neurons via Bicarbonate-Responsive Soluble Adenylyl Cyclase
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Metabolic Communication between Astrocytes and Neurons via Bicarbonate-Responsive Soluble Adenylyl Cyclase

机译：通过碳酸氢盐响应的可溶性腺苷酸环化酶在星形胶质细胞和神经元之间的代谢通讯。

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Astrocytes are proposed to participate in brain energy metabolism by supplying substrates to neurons from their glycogen stores and from glycolysis. However, the molecules involved in metabolic sensing and the molecular pathways responsible for metabolic coupling between different cell types in the brain are not fully understood. Here we show that a recently cloned bicarbonate (HCO 3 -) sensor, soluble adenylyl cyclase (sAC), is highly expressed in astrocytes and becomes activated in response to HCO 3 - entry via the electrogenic NaHCO 3 cotransporter (NBC). Activated sAC increases intracellular cAMP levels, causing glycogen breakdown, enhanced glycolysis, and the release of lactate into the extracellular space, which is subsequently taken up by neurons for use as an energy substrate. This process is recruited over a broad physiological range of [K +] ext and also during aglycemic episodes, helping to maintain synaptic function. These data reveal a molecular pathway in astrocytes that is responsible for brain metabolic coupling to neurons. Choi et al. show that astrocytes express bicarbonate-sensitive soluble adenylyl cyclase that acts as a metabolic sensor of neuronal activity and supplies lactate derived from glycogen breakdown in astrocytes to maintain neuronal activity when alternative energy sources are needed.
机译：星形胶质细胞被提议通过从其糖原存储区和糖酵解作用向神经元提供底物来参与脑能量代谢。但是，关于代谢感测的分子和负责大脑中不同细胞类型之间的代谢偶联的分子途径尚不完全清楚。在这里，我们显示了最近克隆的碳酸氢盐（HCO 3-）传感器，可溶性腺苷酸环化酶（sAC）在星形胶质细胞中高度表达，并响应于HCO 3-通过电致NaHCO 3共转运子（NBC）进入而被激活。活化的sAC会增加细胞内cAMP的水平，导致糖原分解，糖酵解增强和乳酸释放到细胞外空间，随后被神经元吸收并用作能量底物。该过程在广泛的[K +] ext生理范围内以及在血糖发作期间募集，有助于维持突触功能。这些数据揭示了星形胶质细胞中的一种分子途径，该途径负责大脑代谢与神经元的耦合。崔等。研究表明，星形胶质细胞表达碳酸氢盐敏感的可溶性腺苷酸环化酶，该酶充当神经元活性的代谢传感器，并在需要替代能源时，提供星形胶质细胞中糖原分解产生的乳酸以维持神经元活性。

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