Pellerin L, Pellegri G, Bittar P G, Charnay Y, Bouras C, Martin J L, Stella N, Magistretti P J
Institut de Physiologie, Université de Lausanne, Switzerland.
Dev Neurosci. 1998;20(4-5):291-9. doi: 10.1159/000017324.
Mounting evidence from in vitro experiments indicates that lactate is an efficient energy substrate for neurons and that it may significantly contribute to maintain synaptic transmission, particularly during periods of intense activity. Since lactate does not cross the blood-brain barrier easily, blood-borne lactate cannot be a significant source. In vitro studies by several laboratories indicate that astrocytes release large amounts of lactate. In 1994, we proposed a mechanism whereby lactate could be produced by astrocytes in an activity-dependent, glutamate-mediated manner. Over the last 2 years we have obtained further evidence supporting the notion that a transfer of lactate from astrocytes to neurons might indeed take place. In this article, we first review data showing the presence of mRNA encoding for two monocarboxylate transporters, MCT1 and MCT2, in the adult mouse brain. Second, by using monoclonal antibodies selectively directed against the two distinct lactate dehydrogenase isoforms, LDH1 and LDH5, a specific cellular distribution between neurons and astrocytes is revealed which suggests that a population of astrocytes is a lactate 'source' while neurons may be a lactate 'sink'. Third, we provide biochemical evidence that lactate is interchangeable with glucose to support oxidative metabolism in cortical neurons. This set of data is consistent with the existence of an activity-dependent astrocyte-neuron lactate shuttle for the supply of energy substrates to neurons.
越来越多的体外实验证据表明，乳酸是神经元有效的能量底物，并且它可能对维持突触传递有显著贡献，特别是在高强度活动期间。由于乳酸不易穿过血脑屏障，血源性乳酸不可能是其重要来源。几个实验室的体外研究表明，星形胶质细胞会释放大量乳酸。1994年，我们提出了一种机制，即星形胶质细胞可以通过依赖于活动的、谷氨酸介导的方式产生乳酸。在过去两年里，我们获得了更多证据支持星形胶质细胞向神经元确实会发生乳酸转移这一观点。在本文中，我们首先回顾显示成年小鼠大脑中编码两种单羧酸转运体MCT1和MCT2的mRNA存在的数据。其次，通过使用选择性针对两种不同乳酸脱氢酶同工型LDH1和LDH5的单克隆抗体，揭示了神经元和星形胶质细胞之间特定的细胞分布，这表明一部分星形胶质细胞是乳酸“源”，而神经元可能是乳酸“汇”。第三，我们提供了生化证据，证明乳酸与葡萄糖可相互替代以支持皮质神经元的氧化代谢。这组数据与存在一种依赖于活动的星形胶质细胞-神经元乳酸穿梭机制以向神经元供应能量底物的观点一致。
