Pellerin L, Pellegri G, Martin J L, Magistretti P J
Institut de Physiologie et Laboratoire de Recherche du Service de Neurologie du Centre Hospitalier Universitaire Vaudois, Faculté de Médecine, Université de Lausanne, 7 rue du Bugnon, 1005 Lausanne, Switzerland.
Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3990-5. doi: 10.1073/pnas.95.7.3990.
Under particular circumstances like lactation and fasting, the blood-borne monocarboxylates acetoacetate, beta-hydroxybutyrate, and lactate represent significant energy substrates for the brain. Their utilization is dependent on a transport system present on both endothelial cells forming the blood-brain barrier and on intraparenchymal brain cells. Recently, two monocarboxylate transporters, MCT1 and MCT2, have been cloned. We report here the characterization by Northern blot analysis and by in situ hybridization of the expression of MCT1 and MCT2 mRNAs in the mouse brain. In adults, both transporter mRNAs are highly expressed in the cortex, the hippocampus and the cerebellum. During development, a peak in the expression of both transporters occurs around postnatal day 15, declining rapidly by 30 days at levels observed in adults. Double-labeling experiments reveal that the expression of MCT1 mRNA in endothelial cells is highest at postnatal day 15 and is not detectable at adult stages. These results support the notion that monocarboxylates are important energy substrates for the brain at early postnatal stages and are consistent with the sharp decrease in blood-borne monocarboxylate utilization after weaning. In addition, the observation of a sustained intraparenchymal expression of monocarboxylate transporter mRNAs in adults, in face of the seemingly complete disappearance of their expression on endothelial cells, reinforces the view that an intercellular exchange of lactate occurs within the adult brain.
在哺乳和禁食等特殊情况下，血液中的单羧酸酯类物质，如乙酰乙酸、β-羟基丁酸和乳酸，是大脑重要的能量底物。它们的利用依赖于构成血脑屏障的内皮细胞以及脑实质内脑细胞上存在的一种转运系统。最近，两种单羧酸转运蛋白，即MCT1和MCT2，已被克隆出来。我们在此报告通过Northern印迹分析和原位杂交对小鼠脑中MCT1和MCT2 mRNA表达的特征研究。在成年小鼠中，两种转运蛋白的mRNA在皮质、海马体和小脑中均高度表达。在发育过程中，两种转运蛋白的表达在出生后第15天左右达到峰值，到30天时迅速下降至成年时观察到的水平。双重标记实验表明，内皮细胞中MCT1 mRNA的表达在出生后第15天最高，在成年阶段则无法检测到。这些结果支持了单羧酸酯类在出生后早期是大脑重要能量底物的观点，并且与断奶后血液中单羧酸酯类利用的急剧下降相一致。此外，尽管内皮细胞上单羧酸转运蛋白mRNA的表达似乎完全消失，但在成年小鼠脑实质中观察到其持续表达，这进一步强化了成年大脑内存在乳酸细胞间交换的观点。
