How astrocytes feed hungry neurons

For years glucose was thought to constitute the sole energy substrate for neurons; it was believed to be directly provided to neurons via the extracellular space by the cerebral circulation. It was recently proposed that in addition to glucose, neurons might rely on lactate to sustain their activity. Therefore, it was demonstrated that lactate is a preferred oxidative substrate for neurons not only in vitro but also in vivo. Moreover, the presence of specific monocarboxylate transporters on neurons as well as on astrocytes is consistent with the hypothesis of a transfer of lactate from astrocytes to neurons. Evidence has been provided for a mechanism whereby astrocytes respond to glutamatergic activity by enhancing their glycolytic activity, resulting in increased lactate release. This is accomplished via the uptake of glutamate by glial glutamate transporters, leading to activation of the Na+/K+ ATPase and a stimulation of astrocytic glycolysis. Several recent observations obtained both in vitro and in vivo with different approaches have reinforced this view of brain energetics. Such an understanding might be critically important, not only because it forms the basis of some classical functional brain imaging techniques but also because several neurodegenerative diseases exhibit diverse alterations in energy metabolis

Cellular Bases of Brain Energy Metabolism and Their Relevance to Functional Brain Imaging: Evidence for a Prominent Role of Astrocytes

Survey of Brain Energy Metabolism at the Organ and Regional Level

Glutamate reduces glucose utilization while concomitantly enhancing AQP9 and MCT2 expression in cultured rat hippocampal neurons

The excitatory neurotransmitter glutamate has been reported to have a major impact on brain energy metabolism. Using primary cultures of rat hippocampal neurons, we observed that glutamate reduces glucose utilization in this cell type, suggesting alteration in mitochondrial oxidative metabolism. the aquaglyceroporin AQP9 and the monocarboxylate transporter MCT2, two transporters for oxidative energy substrates, appear to be present in mitochondria of these neurons. Moreover, they not only co-localize but they interact with each other as they were found to co-immunoprecipitate from hippocampal neuron homogenates. Exposure of cultured hippocampal neurons to glutamate 100 mu M for 1 h led to enhanced expression of both AQP9 and MCT2 at the protein level without any significant change at the mRNA level. in parallel, a similar increase in the protein expression of LDHA was evidenced without an effect on the mRNA level. These data suggest that glutamate exerts an influence on neuronal energy metabolism likely through a regulation of the expression of some key mitochondrial proteins.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Swiss government scholarshipSwiss National FoundationUniversidade Federal de São Paulo, Dept Fisiol, São Paulo, BrazilUniv Lausanne, Dept Physiol, Lab Neuroenerget, Lausanne, SwitzerlandUniversidade Federal de São Paulo, Dept Fisiol, São Paulo, BrazilFAPESP: 10/50349-1Swiss government scholarship: 2011.0188Swiss National Foundation: 31003A-125063Swiss National Foundation: 31003A-140957Web of Scienc

Alzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect

Epidemiological and biochemical studies show that the sporadic forms of Alzheimer's disease (AD) are characterized by the following hallmarks: (a) An exponential increase with age; (b) Selective neuronal vulnerability; (c) Inverse cancer comorbidity. The present article appeals to these hallmarks to evaluate and contrast two competing models of AD: the amyloid hypothesis (a neuron-centric mechanism) and the Inverse Warburg hypothesis (a neuron-astrocytic mechanism). We show that these three hallmarks of AD conflict with the amyloid hypothesis, but are consistent with the Inverse Warburg hypothesis, a bioenergetic model which postulates that AD is the result of a cascade of three events—mitochondrial dysregulation, metabolic reprogramming (the Inverse Warburg effect), and natural selection. We also provide an explanation for the failures of the clinical trials based on amyloid immunization, and we propose a new class of therapeutic strategies consistent with the neuroenergetic selection model

Selective Postsynaptic Co-localization of MCT2 with AMPA Receptor GluR2/3 Subunits at Excitatory Synapses Exhibiting AMPA Receptor Trafficking

MCT2 is the main neuronal monocarboxylate transporter needed by neurons if they are to use lactate as an additional energy substrate. Previous evidence suggested that some MCT2 could be located in postsynaptic elements of glutamatergic synapses. Using post-embedding electron microscopic immunocytochemistry, it is demonstrated that MCT2 is present at postsynaptic density of asymmetric synapses, in the stratum radiatum of both rat hippocampal CA1 and CA3 regions, as well as at parallel fibre-Purkinje cell synapses in mouse cerebellum. MCT2 levels were significantly lower at mossy fibre synapses on CA3 neurons, and MCT2 was almost absent from symmetric synapses on CA1 pyramidal cells. It could also be demonstrated using quantitative double-labeling immunogold cytochemistry that MCT2 and AMPA receptor GluR2/3 subunits have a similar postsynaptic distribution at asymmetric synapses with high levels expressed within the postsynaptic density. In addition, as for AMPA receptors, a significant proportion of MCT2 is located on vesicular membranes within the postsynaptic spine, forming an intracellular pool available for a putative postsynaptic endo/exocytotic trafficking at these excitatory synapses. Altogether, the data presented provide evidence for MCT2 expression in the postsynaptic density area at specific subsets of glutamatergic synapses, and also suggest that MCT2, like AMPA receptors, could undergo membrane traffickin

Assessing the Impact of Supply Chain Integration through an ERP System

Many organizations have implemented Enterprise Resource Planning (ERP) systems, hoping to use the information integration these systems provide to improve process efficiency and effectiveness. In particular, ERP systems may be instrumental in realizing Cooperative Planning, Forecasting, and Replenishment (CPFR). In this paper, we present an experimental approach that will be used to assess the real impact of the implementation of CPFR through an ERP system

Essays Biochem

Energy metabolism is essential for brain function. In recent years, lactate shuttling between astrocytes and neurons has become a fundamental concept of neuroenergetics. However, it remains unclear to what extent this process is critical for different aspects of cognition, their underlying mechanisms, as well as for the signals used to monitor brain activation.Rôle des différents substrats énergétiques pour l'activité cérébral

Étude expérimentale de la reproductibilité spatiale du dépôt d’énergie par claquage laser sous atmosphère contrôlée d’argon par l’effet de focalisation

Le dépôt d’énergie par claquage laser, notamment dans les gaz, est une technique utilisée en spectroscopie optique d’émission afin d’identifier certaines caractéristiques des milieux étudiés (espèces, température, densité électronique...), et également pour l’initiation de déflagration/détonation. La collection de la lumière émise par le plasma est une condition nécessaire pour appliquer la spectroscopie optique d’émission, ce qui impose la connaissance préalable de la position spatiale du claquage laser afin d’assurer une bonne reproductibilité des essais. Malheureusement, la position spatiale du claquage laser peut légèrement se déplacer entre le point focal et la source laser le long de l’axe laser. Ce phénomène est connu mais à notre connaissance n’a jamais fait l’objet d’études spécifiques. Le travail présenté dans cet article a pour objet l’étude de la répartition spatiale du plasma consécutif à l’apport d’énergie par une source laser (longueur d’onde de 532 nm et énergie fixée) dans une enceinte sous atmosphère contrôlée en argon pour deux conditions de focalisation différentes.&nbsp