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

Upregulation of Barrel GABAergic Neurons Is Associated with Cross-Modal Plasticity in Olfactory Deficit

Background: Loss of a sensory function is often followed by the hypersensitivity of other modalities in mammals, which secures them well-awareness to environmental changes. Cellular and molecular mechanisms underlying cross-modal sensory plasticity remain to be documented. Methodology/Principal Findings: Multidisciplinary approaches, such as electrophysiology, behavioral task and immunohistochemistry, were used to examine the involvement of specific types of neurons in cross-modal plasticity. We have established a mouse model that olfactory deficit leads to a whisking upregulation, and studied how GABAergic neurons are involved in this cross-modal plasticity. In the meantime of inducing whisker tactile hypersensitivity, the olfactory injury recruits more GABAergic neurons and their fine processes in the barrel cortex, as well as upregulates their capacity of encoding action potentials. The hyperpolarization driven by inhibitory inputs strengthens the encoding ability of their target cells. Conclusion/Significance: The upregulation of GABAergic neurons and the functional enhancement of neuronal networks may play an important role in cross-modal sensory plasticity. This finding provides the clues for developing therapeuti

Analysis of Area-Specific Expression Patterns of RORbeta, ER81 and Nurr1 mRNAs in Rat Neocortex by Double In Situ Hybridization and Cortical Box Method

BACKGROUND: The mammalian neocortex is subdivided into many areas, each of which exhibits distinctive lamina architecture. To investigate such area differences in detail, we chose three genes for comparative analyses, namely, RORbeta, ER81 and Nurr1, mRNAs of which have been reported to be mainly expressed in layers 4, 5 and 6, respectively. To analyze their qualitative and quantitative coexpression profiles in the rat neocortex, we used double in situ hybridization (ISH) histochemistry and cortical box method which we previously developed to integrate the data of different staining and individuals in a standard three-dimensional space. PRINCIPAL FINDINGS: Our new approach resulted in three main observations. First, the three genes showed unique area distribution patterns that are mostly complementary to one another. The patterns revealed by cortical box method matched well with the cytoarchitectonic areas defined by Nissl staining. Second, at single cell level, RORbeta and ER81 mRNAs were coexpressed in a subpopulation of layer 5 neurons, whereas Nurr1 and ER81 mRNAs were not colocalized. Third, principal component analysis showed that the order of hierarchical processing in the cortex correlates well with the expression profiles of these three genes. Based on this analysis, the dysgranular zone (DZ) in the somatosensory area was considered to exhibit a profile of a higher order area, which is consistent with previous proposal. CONCLUSIONS/SIGNIFICANCE: The tight relationship between the expression of the three layer specific genes and functional areas were revealed, demonstrating the usefulness of cortical box method in the study on the cerebral cortex. In particular, it allowed us to perform statistical evaluation and pattern matching, which would become important in interpreting the ever-increasing data of gene expression in the cortex

Research in Progress: Holistic Climate Service Prototypes for Farmers in Tambuu, Tanzania

Part 3: Southern-Driven Human-Computer InteractionInternational audienceUrgent efforts are needed to address climate change and changing climate variability. Solutions are needed at economic, political, scientific, educational, as well as technological domains. Our previous research in Tambuu, Tanzania, shows that the acute information needs of the community are credible and trustworthy weather information, knowledge in best uses of weather information, and education about best farming practices. Delivering the information for end users in Tambuu is a challenge in itself. Based on these results and following the principles of System Action Design Research, we developed prototypes for future climate services together with local farmers in Tambuu community. These prototypes and our future plans are presented in this research-in-progress paper

Towards Holistic Mobile Climate Services for Farmers in Tambuu, Tanzania

Part 2: Digital Platforms for DevelopmentInternational audienceClimate change and changing climate variability are pressing problems that need urgent solutions, now! Climate change has global consequences, and is already being experienced, mainly by the most vulnerable groups of people in the global south. Research shows that farming activities in the global south are being complicated by added uncertainties in weather. To mitigate the effect of weather uncertainties, there is a need for holistic mobile climate services. We have taken the first step towards the service by finding out the local information needs and current mobile usage patterns in Tambuu village, Tanzania. The results show that climate change is already complicating farmers’ lives and therefore they have urgent need for information on how to prepare and adapt to changing conditions. From the technology perspective, the domination of voice calls and short messages in the current mobile usage limits the adoption of new services. However, modern uses of smart devices for farming activities were also found. Building on this ground, we propose designing climate service prototypes together with local farmers and other relevant stakeholders

Navigating Global Online Market Places (GOMPs) – An ADR Perspective

Part 5: Social Media and Open ComputingInternational audienceGlobal Online Market Places (GOMPs), such as Amazon, Alibaba, Otto, transforms ecommerce. We are moving away from a world of many ecommerce stores to a world populated by a few oligopolies. This create a new competitive situation, not only for the individual firm, but also for countries. Despite the established importance of export to a nation’s economy and the proliferation of the internet today, there are still many companies grappling with taking advantage of the possibilities of e-export. This study is aimed at designing a solution and developing an intervention to mitigate the challenges faced by such companies in Denmark. This research in progress paper reports on the initial activities of the design of a platform intended to be the hub for connecting companies to multiple online market places. This paper sets the frame for the subsequent design, development and evaluation efforts as well as learnings for this research project. Our study extends the conventional view of ADR from a research approach with an organizational purview to one that is amenable to providing practically relevant solutions to national issues

Challenges in Production and Manufacturing Systems Platform Development for Changeable Manufacturing

Part 5: Smart Production for Mass CustomizationInternational audienceDevelopment of platforms for products has proven a successful way to manage and address several challenges related to increasing variety and accelerating product development cycles. Thus, it is natural to assume that platforms may facilitate similar benefits for manufacturing systems, as they are both technical systems. Production and manufacturing systems platform development is, however, still an area of research lacking maturity. Development of platforms in this field comes with a set of challenges not necessarily found in product platform development. Looking towards other fields of research or science may be necessary to address these challenges. This paper aims to study challenges related to production and manufacturing systems platform development and describe how these have been addressed. It does so through an evolving case study based on four projects with an industrial collaborator. This leads to setting the stage for future research on production platforms