Metabolic compartmentalization in the human cortex and hippocampus: evidence for a cell- and region-specific localization of lactate dehydrogenase 5 and pyruvate dehydrogenase.
Metabolic compartmentalization in the human cortex and hippocampus: evidence for a cell- and region-specific localization of lactate dehydrogenase 5 and pyruvate dehydrogenase.
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人皮质和海马中的代谢区室化：乳酸脱氢酶5和丙酮酸脱氢酶的细胞和区域特异性定位的证据。
DOI：
10.1186/1471-2202-8-35
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发表时间：
2007-05-23
期刊：
影响因子：
2.4
通讯作者：
Bouras, Constantin
中科院分区：
文献类型：
--
作者：
Laughton, Jocelyn D.;Bittar, Philippe;Charnay, Yves;Pellerin, Luc;Kovari, Eniko;Magistretti, Pierre J.;Bouras, Constantin
长期以来，葡萄糖一直被认为是大脑能量代谢的主要底物，如果不是唯一底物的话。然而，最近的数据表明，其他分子，如单羧酸盐（主要是乳酸盐和丙酮酸盐）可能是合适的底物。虽然单羧酸盐难以穿过血脑屏障（BBB），但如果在局部产生，这些底物可以取代葡萄糖。生产这些单羧酸所需的两个关键酶系统是催化乳酸和丙酮酸相互转化的乳酸脱氢酶（LDH;EC1.1.1.27）和将丙酮酸不可逆地汇集到线粒体TCA和氧化磷酸化的丙酮酸脱氢酶复合物。在这篇文章中，我们表明，与单克隆抗体适用于死后人脑组织，乳酸脱氢酶（LDH-5，也称为LDHA或LDHM）的典型糖酵解同工酶是选择性地存在于星形胶质细胞，而不是在神经元，而丙酮酸脱氢酶（PDH）主要是在神经元和几乎没有在星形胶质细胞检测。在区域水平上，LDH-5免疫反应性星形胶质细胞的分布是层状的，对应于枕叶皮质和海马中最大2-脱氧葡萄糖摄取的区域。在海马，我们观察到的分布，氧化酶PDH的富集在神经元的皮层和颗粒层的CA 1至CA 4，而糖酵解酶LDH-5的富集在星形胶质细胞的分子层，肺泡和白色物质，揭示不仅细胞，而且区域，选择性分布。事实上，LDH-5的免疫反应性是高的星形胶质细胞和发生在2-脱氧葡萄糖的最高摄取的观察表明，葡萄糖摄取，然后乳酸生产可能主要发生在这些地区。这些观察结果揭示了代谢分离，不仅在细胞，而且在区域水平上，支持星形胶质细胞和神经元之间的代谢区室化的概念，从而星形胶质细胞产生的乳酸可以被神经元氧化。
For a long time now, glucose has been thought to be the main, if not the sole substrate for brain energy metabolism. Recent data nevertheless suggest that other molecules, such as monocarboxylates (lactate and pyruvate mainly) could be suitable substrates. Although monocarboxylates poorly cross the blood brain barrier (BBB), such substrates could replace glucose if produced locally. The two key enzymatiques systems required for the production of these monocarboxylates are lactate dehydrogenase (LDH; EC1.1.1.27) that catalyses the interconversion of lactate and pyruvate and the pyruvate dehydrogenase complex that irreversibly funnels pyruvate towards the mitochondrial TCA and oxydative phosphorylation. In this article, we show, with monoclonal antibodies applied to post-mortem human brain tissues, that the typically glycolytic isoenzyme of lactate dehydrogenase (LDH-5; also called LDHA or LDHM) is selectively present in astrocytes, and not in neurons, whereas pyruvate dehydrogenase (PDH) is mainly detected in neurons and barely in astrocytes. At the regional level, the distribution of the LDH-5 immunoreactive astrocytes is laminar and corresponds to regions of maximal 2-deoxyglucose uptake in the occipital cortex and hippocampus. In hippocampus, we observed that the distribution of the oxidative enzyme PDH was enriched in the neurons of the stratum pyramidale and stratum granulosum of CA1 through CA4, whereas the glycolytic enzyme LDH-5 was enriched in astrocytes of the stratum moleculare, the alveus and the white matter, revealing not only cellular, but also regional, selective distributions. The fact that LDH-5 immunoreactivity was high in astrocytes and occurred in regions where the highest uptake of 2-deoxyglucose was observed suggests that glucose uptake followed by lactate production may principally occur in these regions. These observations reveal a metabolic segregation, not only at the cellular but also at the regional level, that support the notion of metabolic compartmentalization between astrocytes and neurons, whereby lactate produced by astrocytes could be oxidized by neurons.
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影响因子：
2.8
作者：
CHARNAY, Y;GOLAZ, J;BOURAS, C
通讯作者：
BOURAS, C
影响因子：
56.9
作者：
DAWSON, DM;KAPLAN, NO;GOODFRIEND, TL
通讯作者：
GOODFRIEND, TL
DOI：
10.1073/pnas.83.4.1140
发表时间：
1986-02-01
影响因子：
11.1
作者：
FOX, PT;RAICHLE, ME
通讯作者：
RAICHLE, ME
DOI：
10.1073/pnas.0307458100
发表时间：
2004-01-13
影响因子：
11.1
作者：
Ido, Y;Chang, K;Williamson, JR
通讯作者：
Williamson, JR
影响因子：
6.3
作者：
FOX, PT;MINTUN, MA;RAICHLE, ME
通讯作者：
RAICHLE, ME