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

Harmonisering models for the Dutch Nature Policy Assessment Office

This report describes the proposal for the set of (ecological) models to be used as the prime tools in the analysis of the Nature, Landscape and Woodland policy by the Dutch Nature Policy Assessment Office. The identification of the key models is regarded as the first step towards the construction of a consistent set of well-tuned models, enabling a high-quality policy analysis by the Nature Policy Assessment Office. The eventual choice for the key models was based on the results of a thorough inventory of ecological models brought face to face with the demands on the use of policy analysis tools by the Assessment Office. Models for scenario construction and analysis of social aspects were beyond the scope of the present study, while abiotic environmental models are described only when relevant for the input of the ecological models mentioned.Dit rapport beschrijft het voorstel voor de inrichting van het kerninstrumentarium van het Natuurplanbureau voor fysieke aspecten van Natuur (waaronder terrestrisch, aquatisch en marien), Landschap en Bos. Scenario modellen, abiotische modellen en modellen voor het sociale domein zijn buiten beschouwing gelaten, hoewel de toeleverende abiotische modellen wel behandeld zijn voor zover deze informatie leveren aan de beschouwde groep van (ecologische) modellen. De samenstelling van een kerninstrumentarium is de eerste stap die uiteindelijk zal moeten resulteren in de bouw van een gestroomlijnde, consistente en samenhangende set van modellen en/of modelketens, waarmee het planbureau adequaat invulling kan geven aan haar functies. De gemaakte keuze is gebaseerd op de gegevens van een uitgebreide inventarisatie van bestaande en in ontwikkeling zijnde modellen. Deze modelbeschrijvingen zijn geconfronteerd met de modeleisen zoals die voor het vervullen van de natuurplanbureaufuncties noodzakelijk worden geacht

Harmonisering models for the Dutch Nature Policy Assessment Office

Dit rapport beschrijft het voorstel voor de inrichting van het kerninstrumentarium van het Natuurplanbureau voor fysieke aspecten van Natuur (waaronder terrestrisch, aquatisch en marien), Landschap en Bos. Scenario modellen, abiotische modellen en modellen voor het sociale domein zijn buiten beschouwing gelaten, hoewel de toeleverende abiotische modellen wel behandeld zijn voor zover deze informatie leveren aan de beschouwde groep van (ecologische) modellen. De samenstelling van een kerninstrumentarium is de eerste stap die uiteindelijk zal moeten resulteren in de bouw van een gestroomlijnde, consistente en samenhangende set van modellen en/of modelketens, waarmee het planbureau adequaat invulling kan geven aan haar functies. De gemaakte keuze is gebaseerd op de gegevens van een uitgebreide inventarisatie van bestaande en in ontwikkeling zijnde modellen. Deze modelbeschrijvingen zijn geconfronteerd met de modeleisen zoals die voor het vervullen van de natuurplanbureaufuncties noodzakelijk worden geacht.This report describes the proposal for the set of (ecological) models to be used as the prime tools in the analysis of the Nature, Landscape and Woodland policy by the Dutch Nature Policy Assessment Office. The identification of the key models is regarded as the first step towards the construction of a consistent set of well-tuned models, enabling a high-quality policy analysis by the Nature Policy Assessment Office. The eventual choice for the key models was based on the results of a thorough inventory of ecological models brought face to face with the demands on the use of policy analysis tools by the Assessment Office. Models for scenario construction and analysis of social aspects were beyond the scope of the present study, while abiotic environmental models are described only when relevant for the input of the ecological models mentioned.CU