首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >Expression of monocarboxylate transporter mRNAs in mouse brain: Support for a distinct role of lactate as an energy substrate for the neonatal vs. adult brain
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Expression of monocarboxylate transporter mRNAs in mouse brain: Support for a distinct role of lactate as an energy substrate for the neonatal vs. adult brain

机译:单羧酸转运蛋白mRNA在小鼠脑中的表达:支持乳酸作为新生儿与成年脑的能量底物的独特作用

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摘要

Under particular circumstances like lactation and fasting, the blood-borne monocarboxylates acetoacetate, β-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.
机译:在诸如哺乳和禁食之类的特殊情况下,血源性单羧酸酯乙酰乙酸酯,β-羟基丁酸酯和乳酸是大脑重要的能量底物。它们的利用取决于存在于形成血脑屏障的内皮细胞和实质内脑细胞上的转运系统。最近,已经克隆了两个单羧酸盐转运蛋白MCT1和MCT2。我们在这里报告通过Northern印迹分析和小鼠大脑中MCT1和MCT2 mRNA表达的原位杂交表征。在成年人中,两种转运蛋白的mRNA均在皮质,海马和小脑中高表达。在发育过程中,两种转运蛋白的表达均在出生后第15天左右达到峰值,并在成年人中观察到的水平迅速下降了30天。双重标记实验表明,MCT1 mRNA在内皮细胞中的表达在出生后第15天最高,而在成年阶段则无法检测到。这些结果支持这样的观点,即单羧酸盐是出生后早期大脑的重要能量底物,并且与断奶后血液中单羧酸盐的利用率急剧下降相一致。另外,观察到成年人中单羧酸盐转运蛋白mRNA的持续实质内表达,面对它们在内皮细胞上的表达似乎完全消失的事实,加强了这样的观点,即在成年人的大脑中发生乳酸的细胞间交换。

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