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

Environmental forcing of phytoplankton in a Mediterranean estuary (Guadiana Estuary, southwestern Iberia): a decadal of anthropogenic and climatic influences

Phytoplankton seasonal and interannual variability in theGuadiana upper estuarywas analyzed during 1996–2005, a period that encompassed a climatic controlled reduction in river flow that was superimposed on the construction of a dam. Phytoplankton seasonal patterns revealed an alternation between a persistent light limitation and episodic nutrient limitation. Phytoplankton succession, with early spring diatom blooms and summer–early fall cyanobacterial blooms, was apparently driven by changes in nutrients, water temperature, and turbulence, clearly demonstrating the role of river flow and climate variability. Light intensity in the mixed layer was a prevalent driver of phytoplankton interannual variability, and the increased turbidity caused by the Alqueva dam construction was linked to pronounced decreases in chlorophyll a concentration, particularly at the start and end of the phytoplankton growing period. Decreases in annual maximum and average abundances of diatoms, green algae, and cyanobacteria were also detected. Furthermore, chlorophyll a decreases after dam filling and a decrease in turbidity may point to a shift from light limitation towards a more nutrient-limited mode in the near future