5 research outputs found
Metabolic compartmentalization in the human cortex and hippocampus: evidence for a cell- and region-specific localization of lactate dehydrogenase 5 and pyruvate dehydrogenase
BACKGROUND: 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. RESULTS: 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. CONCLUSION: 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
Trimeter and Senarius - Rosa Maria D'Angelo: Fra trimetro e senario giambico. Ricerche di metrica greca e latina. (Biblioteca Athena, 25.) Pp. 127. Rome: Edizioni dell'Ateneo, 1983. Paper.
Biochemical characterization of anti-LDH-5 (A) and anti-PDH (B) monoclonal antibodies by SDS-PAGE
<p><b>Copyright information:</b></p><p>Taken from "Metabolic compartmentalization in the human cortex and hippocampus: evidence for a cell- and region-specific localization of lactate dehydrogenase 5 and pyruvate dehydrogenase"</p><p>http://www.biomedcentral.com/1471-2202/8/35</p><p>BMC Neuroscience 2007;8():35-35.</p><p>Published online 23 May 2007</p><p>PMCID:PMC1899510.</p><p></p> 1A) 1, rabbit heart; 2, rabbit muscle; 3, human LDH-1 and 4, human hippocampal extracts. 1B) 1–3, human hippocampal extracts (2, mitochondrial fraction, 3, cytosolic fraction), 4–6, human occipital cortex extracts(5, mitochondrial fraction, 6, cytosolic fraction), 7, PDH from porcine heart and 8, LDH-5 from rabbit muscle (absence of positive band at 35 kDa omitted)
PDH like (A, C) and LDH-5 like (B, D) immunoreactivity in the human hippocampus at low (A, B) and high (C, D) magnification
<p><b>Copyright information:</b></p><p>Taken from "Metabolic compartmentalization in the human cortex and hippocampus: evidence for a cell- and region-specific localization of lactate dehydrogenase 5 and pyruvate dehydrogenase"</p><p>http://www.biomedcentral.com/1471-2202/8/35</p><p>BMC Neuroscience 2007;8():35-35.</p><p>Published online 23 May 2007</p><p>PMCID:PMC1899510.</p><p></p> Microphotograph E shows double immunolabeling (PDH, granular neuron, blue, ◆; LDH-5, protoplastmic astrocyte, brown, *). Scale A, B; 500 μm; C, D: 25 μm and E: 20 μm. Abbreviations SP: stratumpyramidale, SM: stratum moleculare and SG: stratum granulosum. Scale (A), B; 500 μm; (C), D: 25 μm and E: 20 μm