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Dr. Chris Palmer presentation: Brain Energy, The metabolic Theory of Mental IllnessCerebral function is associated with exceptionally high metabolic activity, and requires continuous supply of oxygen and nutrients from the blood stream. Since the mid-twentieth century the idea Water weight reduction tricks brain energy metabolism is coupled to neuronal activity has emerged, and a number of studies supported this hypothesis.
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Data recently acquired in our laboratory Sonnay Enwrgy al. The brain can consume several substrates, such as lactate Bouzier et al.
Uptake of monocarboxylates, such as brakn, pyruvate, and ketone bodies, is mediated Ejergy monocarboxylate transporters MCT along Enerby the co-transport of one 1 H for each molecule. Metabollism isoform MCT1 is Eenrgy in the endothelial cells and Enefgy astrocytes reviewed Boosts digestive energy levels Pierre and Pellerin,MCT4 in astrocytes and Metabllism in neurons Bergersen et al.
In braiin brain Enervy, glucose transport and utilization healtth predominantly mediated Onion seasoning ideas facilitated diffusion through glucose transporters GLUT1 and GLUT3 that belong Metabolism Boosting Fat Burners the Eergy Carrier Family 2 SLC2.
GLUT1 is present in all brain cells, Eneryg high anc in astrocytes and Heightened Alertness cells of the capillaries, but less in neurons braim in Maher et al. In contrast, GLUT3 expression is almost restricted to neurons Maher et al. GLUT1 is thus the main carrier involved in the import of glucose into the brain from the blood, and its apparent affinity for glucose transport is lower than that of GLUT3 discussed in Simpson et al.
These two facilitative carriers mediate energy-independent transport of glucose bi-directionally along a concentration gradient, which is maintained by continuous phosphorylation of intracellular glucose by the glycolytic enzyme hexokinase, and exist in sufficient density to ensure that glucose transport is not rate-limiting for CMR glc Gruetter et al.
GLUT4 in neurons Ashrafi et al. However, GLUT2 and GLUT4 are carriers involved in specific functions in certain brain areas, and are likely to have a minor role on glucose uptake for cellular fueling. After entering the cells, glucose is converted via glycolysis to two molecules of pyruvate with net formation of 2 ATP and 2 NADH in the cytosol.
Acetyl-CoA condensates with oxaloacetate entering therefore oxidative metabolism via the tricarboxylic TCA cycle. Each turn of the TCA cycle yields 3 NADH, 1 FADH 2 and 1 GTP molecules. As each NADH and FADH 2 molecules generates 2. Oxidation of glucose-derived pyruvate through the TCA cycle not only provides the bulk of energy produced to support cerebral function reviewed in Hertz and Dienel,but also involves the generation of de novo amino acids, namely glutamate reviewed in Gruetter, Neurons extensively release glutamate and need therefore a replenishment system to ensure adequate neurotransmitter levels.
Namely, synthesis of de novo oxaloacetate from pyruvate is catalyzed by the glial-specific enzyme pyruvate carboxylase PC; Gamberino et al. Oxaloacetate formed through pyruvate carboxylation condensates with acetyl-CoA to produce new glutamate molecules Waagepetersen et al.
In addition, under low acetyl-CoA concentration, pyruvate can be produced cataplerotically from TCA cycle intermediates pyruvate recycling : from oxaloacetate, mediated by the combined action of phosphoenolpyruvate carboxykinase PEPCK and pyruvate kinase PK; Cruz et al.
Once glutamate is taken by astrocytes, it can be converted to glutamine in an energy-dependent manner via the glial-specific enzyme, glutamine synthetase GS; Derouiche and Frotscher, Glutamine is then transported to neurons via the System N transporter SN1 in astrocytes Chaudhry et al.
Glutamate can also re-enter the TCA cycle Qu et al. Consequently, the glutamate-glutamine cycle is not a stoichiometric process, as a number of amino acid molecules can be used in other metabolic pathways depending on cellular requirements McKenna, Glutamine can diffuse out of the brain parenchyma and be used for ammonia detoxification Zwingmann and Leibfritz, In addition, glutamate can have other fates than being converted to glutamine, such as formation of GABA and glutathione, and be synthetized from other substrates than glucose, namely lactate or ketone bodies.
Amino acids can also be used for biosynthetic pathways and derived from protein degradation McKenna, ; Figure 1. Figure 1. Schematic representation of possible pathways mediating neurometabolic coupling. Upon action potential glutamate is released in the synaptic cleft and activates the post-synaptic glutamate receptors mGluR, NMDA, AMPA, and kainate.
Glial glutamate is then converted to glutamine by glutamine synthetase GSan energy-dependent reaction, and is shuttled back to neurons via system N transporter SN1 and system A transporter SA1,2. In neuron, glutamine is hydrolyzed by glutaminase GLS into glutamate that is packed into vesicles by VGLUT for further glutamate release.
Glutamate uptake into astrocytes is associated with glucose transport from plasma via GLUT1, and both glycolysis and oxidative metabolism via pyruvate dehydrogenase PDH take place. Glucose is also transported into neurons via GLUT3, where it also undergoes non-oxidative and oxidative metabolism.
Produced-glutamate can re-enter the TCA cycle i. In astrocytes, pyruvate can be produced cataplerotically either from oxaloacetate, mediating the combined action of phosphoenolpyruvate carboxykinase PEPCK and pyruvate kinase PKor from malate by the malic enzyme ME; i.
Glycolytic-derived pyruvate is converted to lactate by lactate dehydrogenase LDH and exchanged between neurons and astrocytes through monocarboxylate transporters MCT1,4 and MCT2. In astrocytes, pyruvate carboxylase PC produces oxaloacetate from pyruvate in mediating CO 2 fixation in an energy-dependent manner.
Oxaloacetate condensates then with acetyl-CoA to produce de novo molecules of glutamate. The left and right cells represent an astrocyte and a neuron, respectively. The difference in TCA cycle size reflects the fact that neurons are more oxidative than astrocytes. The red circle is a blood vessel, the surrounding darker layer represents the endothelial cells and the thicker outer line is the smooth muscle cells or pericytes.
Word in bold red and bold purple corresponds to energy-producing and consuming processes, respectively. Enzymes are in gray italic. The term astrocyte originates etymologically from the Greek words astron star and cyte cell. They belong to the general group of macroglia cells Kettenmann and Verkhratsky,where glia is derived from the Greek word gliok glue.
Several cytological studies on rats Kacem et al. Perisynaptic processes largely express glutamate transporters EAAT1 and EAAT2while endfeet are more specialized in nutrient uptake and express large amounts of glucose transporters GLUT1; Iadecola and Nedergaard, Therefore, the etymology reflects what astrocytes have traditionally been considered, satellite housekeeping cells of the brain, whose sole purpose is to serve neuronal cells in creating a favorable environment for the neurons to function efficiently.
In this conventional view, astrocytes control pH and local ion homeostasis, deliver nutrients and clean neuronal waste Nedergaard et al. However, the role of astrocytes extends beyond physically supporting neurons. Interconnected via gap junctions, astrocytes form a complex functional network that detects and modulates neuronal activity, integrates and transmits surrounding signals, controls brain vasculature for nutrient delivery, and regulates and metabolizes energy substrates.
Astrocytes transport glucose via GLUT1 transporters reviewed in Maher et al. Astrocytes are, therefore, prone to aerobic glycolysis Barros and Deitmer, and early studies have supported that glycolysis can be stimulated by neuronal activity Kasischke et al.
Recently, using the genetically encoded fluorescence resonance energy transfer FRET lactate sensor Laconic, a lactate gradient from astrocytes to neurons was demonstrated in vivo Mächler et al.
On the other hand, neurons constantly degrade PFKFB3 Almeida et al. The study by Sibson et al. in the rat brain suggesting stoichiometry between neuronal glucose oxidation and the glutamate-glutamine cycle rate Sibson et al.
However, this hypothesis did not consider or exclude stimulation of glial oxidative metabolism to support increased neurotransmission rates. Yet, hexokinase was shown to be highly expressed in neurons as compared to astrocytes Lundgaard et al. In line with this, it was reported that increased glycolysis occurs for example in nerve terminals of bicuculline-treated rats Patel et al.
Although glycolytic activity is higher in glia than in neurons, astrocytes express an important number of enzymes involved in the TCA cycle, suggesting substantial oxidative capacity. Moreover, an important amount of small mitochondria was detected in the fine astrocytic processes Derouiche et al.
Consistent with glial metabolic activation by neuronal activity Eriksson et al. A few in vivo studies have investigated the metabolic involvement of glia during neuronal activation. In particular, autoradiography studies using the glial-specific energy substrate acetate demonstrated increased glial oxidative metabolism during both acoustic Cruz et al.
Similarly, positron emission tomography PET along with [1- 11 C]acetate infusion showed increased astrocytic oxidative metabolism during infraorbital nerve stimulation of anesthetized rats and visual stimulation in humans Wyss et al.
Using dual photon fluorescence confocal microscopy, Lind et al. With the same methodology the glial activation map was reported to resemble that of neurons during rat paw stimulation, suggesting both neuronal, and glial topographical representation of the body in the cortex Ghosh et al.
While these techniques present high spatial resolution, they are associated with some disadvantages, such as the need of radioactive tracers and ionizing radiations PET, autoradiographyinvasiveness dual photon fluorescence confocal microscopy, FRET, autoradiographypotential cellular toxicity FRETthe lack of absolute quantification in the case of FRET as signal magnitude directly rely on the number of molecules of interest binding the sensorand the lack of chemical specificity PET, autoradiography for providing quantitative information on metabolic pathways underlying oxidative metabolism.
Currently, the development of tracers detectable by MRS, such as 13 C-labeled substrates, the improvement of detection modalities Henry et al. In particular direct detection of 13 C-labeled compounds 13 C MRS provides quantitative assessment of major metabolic pathways including glycolysis, TCA cycle, glutamate-glutamine cycle and pyruvate carboxylase Gruetter et al.
Direct detection of 13 C-labeled compounds is a technique that has been robustly implemented and can be applied to small animal metabolism studies in the whole brain Duarte et al. Nuclear magnetic resonance NMR is a non-ionizing and non-invasive technique based on the magnetic properties of spin-containing nuclei.
This methodology can be used in both clinical settings e. However, in most animal applications it requires anesthesia, which can modify the coupling between neuronal activity, brain metabolism and vascular regulation of blood flow Masamoto and Kanno, ; Sonnay et al.
Several nuclei can be used to investigate brain metabolism, notably 1 H, 31 P, or 13 C.
: Energy metabolism and brain health| Brain Energy: The Metabolic Theory of Mental Illness | Psychology Today Canada | Notably, V dil dilutes glial acetyl-CoA 13 C labeling relative to its precursor pyruvate. As the position C4 of glutamate and glutamine only receives labeling from acetyl-CoA, dilution at this point would lead to a lower steady-state C4 labeling. Since glutamate and glutamine are mainly present in neurons and glia, respectively, V dil is also responsible for lower FE of position C4, C3, and C2 of glutamine compared to glutamate. However, the effect of V dil on enhancing the labeling difference between glutamate and glutamine is counteracted by V NT , which represents the glutamate-glutamine cycle. The faster the rate of V NT , the more similar will be the labeling of glutamate and glutamine. Note that V dil in glial acetyl-CoA can result in glutamine C2 being similar or larger than glutamine C4, which has been observed in some studies discussed in Duarte et al. V ex represents an exchange between two putative glutamine pools, one of which is not released to neurons and may account for a continuous slow increase in FE over time Duarte and Gruetter, V ex can be in exchange with a 1 H MR invisible but 13 C labeled glutamine pool Hancu and Port, or with unlabeled amino acids from the blood i. This second glutamine pool could be associated with biosynthetic pathways, which have rates much slower than mitochondrial energy metabolism McKenna, The effect of V ex is in practice observable near the end of an experiment, when the labeling of glutamine still increases, while glutamate is at steady-state. Therefore, if mitochondrial metabolism is faster than glycolysis, oxidation of additional substrates, such as lactate, must occur under certain conditions Sonnay et al. In resting human brain, however, the brain exports lactate to the blood stream discussed in Dienel, The above descriptions are purely indicative of what happens for each flux independently. Experimental data is a linear combination of many fluxes, which will adjust during fitting process to best describe the turnover curves. The first 13 C MRS data acquired in vivo upon stimulus-induced brain activity were modeled using a one-compartment model and reported a marked increase in total TCA cycle activity in the somatosensory cortex of stimulated rats compared to rest Hyder et al. The following experiment consisted on measuring neuronal CMR glc ox under three different anesthesia-induced activity states, namely pentobarbital deep , α-chloralose moderate and morphine light Sibson et al. According to this model, no stimulation of oxidative metabolism should occur in glia, in contrast to neurons. Later several studies in rat brain Patel et al. However, it should be noted that constraining the value of V PC to V GS and V TCA g to the total V TCA implies an effective coupling between glial oxidative metabolism and neuronal function. Indeed, the astrocytic processes engulfing synapses are capable of sensing increased synaptic activity Iadecola and Nedergaard, ; Cheung et al. The 13 C MRS study by Gruetter et al. Using a similar model, glial oxidation and pyruvate carboxylase activity was shown to significantly contribute also to total glucose oxidation in awake animals Oz et al. Recently, our group further addressed the issue of glial and neuronal oxidative metabolism coupled to neuronal activity. In particular, we first measured the cortical changes in metabolic fluxes induced by electrical stimulation of the four paws of rats. We observed a similar increase in absolute terms of both glial and neuronal oxidative metabolism resulting from the increase in glutamate-glutamine cycle rate Figure 5 ; Sonnay et al. Interestingly in this study, as well as in Patel et al. Indeed Patel and Tilghman reported that glutamate can stimulate pyruvate carboxylation Patel and Tilghman, Instead, glutamate could be oxidized in astrocytes to compensate for the high cost of glutamate uptake during neurotransmission McKenna, Figure 5. Relation of estimated total, neuronal and glial glucose oxidative metabolism to the glutamate-glutamine cycle in the rat cortex anesthetized with α-chloralose originally reported in Sonnay et al. Average fluxes across the resting in blue and stimulated in red group are shown with associated SD. In the study by Sonnay et al. However, the simulations by DiNuzzo et al. are still unable to account for substantial V TCA g in cases of low glutamate-glutamine cycle rate. To summarize, in addition to the proposed coupling of neuronal oxidative metabolism and neurotransmission, astrocytes increase their oxidative metabolism too, resulting in a large production of ATP. It is, therefore, important to investigate the exact fate of the ATP produced. In this context, the ATP produced in glia might notably support blood flow regulation Zonta et al. Glycogenolysis might moreover provide energy to support neurotransmission i. Brain vasculature is rich in arterioles and fine capillaries Reina-De La Torre et al. In this context astrocytes and neurons are presumed to play a key role in modulating CBF to match energy demands. In astrocytes, activation of mGluR by glutamate triggers the translocation of the α-subunit of the receptors to phospholipase C PLC mediating the conversion of GTP to GDP Bockaert et al. In neurons, cyclooxygenase COX converts AA into prostaglandins E 2 PGE 2 leading to vessel dilation Wang et al. In astrocytes, AA can be converted either to PGE 2 by COX Zonta et al. If AA is converted into hydroxyeicosatetraenoic acid HETE by ω-hydroxylase in pericytes, it will cause vasoconstriction Metea and Newman, New line of evidence suggest moreover that the astrocytic production of PGE 2 might be dependent on glutathione levels Howarth et al. In neurons activation of ionotropic glutamate receptors located on the post-synaptic zone i. Interaction of NO with soluble guanylate cyclase sGC triggers cGMP dependent vasodilation mechanisms Laranjinha et al. Intracellular adenosine can be released extracellularly by nucleoside transporters Iliff et al. Increase in cAMP leads to vasodilation and inhibits the vasoconstrictive effects of HETE Koehler et al. Figure 6. Schematic representation of possible signaling pathways mediating neurovascular coupling. Arachidonic acid AA is then produced by phospholipase A 2 PLA 2. In astrocytes AA can be converted either to prostaglandins E 2 PGE 2 by cyclooxygenase COX or to epoxeicosatrienoic acids EET by epoxygenase for vasodilation. If AA is converted into hydroxyeicosatetraenoic acid HETE by ω-hydroxylase, it will lead to vasoconstriction. In pericytes and smooth muscle cells NO interacts with the soluble guanylate cyclase sGC for cGMP- dependent vasodilation mechanisms. Intracellular adenosine can be transported by the nucleoside transporters to activate the adenosine receptors AR for cAMP-dependent vasodilation mechanisms via adenylate cyclase and inhibiting the vasoconstrictive effects of HETE. Lactate can inhibit the astrocytic prostaglandin transporter PGT -mediated PGE-lactate exchange, increasing therefore extracellular PGE 2 concentration. Astrocytes can modulate synaptic plasticity in releasing vesicles containing glutamate, D-serine, ATP and neurotrophic factors in an ATP-dependent manner. Glutathione is produced in astrocytes and can be released through multidrug resistance proteins MRP mediating ATP hydrolysis. Release of ascorbate mediate non-hydrolytic ATP binding to volume-sensitive organic osmolyte-anion channel VSOAC and is stimulated by glutamate. The dashed line represents vasodilation and the dotted line vasoconstriction. Local CBF response could be immediately regulated by fast ms feed-forward mechanisms directly related to neuronal activity e. Although astrocytes do not generate action potentials per se they can actively modulate synaptic transmission and neuronal synchronization in mediating notably the release of vesicles-containing neurotransmitters and neuromodulators, such as glutamate, ATP, adenosine, and D-serine. In the extracellular space ATP can be converted to adenosine by the dephosphorylating action of the ectonucleotidase anchored at the plasma membrane Joseph et al. D-serine that can be released from astrocytes was also shown to modulate electrical neurotransmission by acting at the glycine binding site of NMDA receptor Stevens et al. Interestingly, the number of astrocytic processes, as well as their contact with active synapses, are stimulated by extracellular glutamate and also involve actin-dependent mechanisms Cornell-Bell et al. Yet, the cooperative action of astrocytes in culture was shown to protect neurons against ROS toxicity Desagher et al. The thiol group of the glutathione molecule acts as an important electron donor. While both neurons and astrocytes synthesize glutathione, neuronal glutathione levels are higher in the presence of astrocytes Dringen et al. Glutathione transport across cells is notably mediated by multidrug resistance proteins MRP that belong to the subgroup ABCC of the ATP-binding cassette transporters, which mediate passage via ATP hydrolysis Borst and Elferink, ; Dringen and Hirrlinger, ; Figure 5. Activation of astrocytic glutamate receptors was shown to translocate nuclear factor-erythroid 2-realted factor-2 Nrf2 present in lower concentrations in neurons into the nucleus and to trigger the expression of antioxidant genes, notably related to glutathione metabolism Jimenez-Blasco et al. Astrocytes synthesize large amount of hydrogen sulfide, which was demonstrated to not only have neuroprotective properties Lee et al. Ascorbate is also another important antioxidant anion in the brain and glutamate was demonstrated to stimulate its release from astrocytes Wilson et al. Astrocytes are responsible for the recycling of the neuronal extracellularly released dehydroascorbic acid the oxidized form of ascorbate into ascorbate, which can be exported to neurons Covarrubias-Pinto et al. Extracellular transport of ascorbate from astrocytes is believed to be mediated by volume-sensitive organic osmolyte-anion channel VSOAC that requires non-hydrolytic ATP binding Jackson et al. Considering the fact that efficacy of the mechanisms stimulated by astrocytic glutamate uptake depends on the density of the transporters at the plasma membrane Robinson, , efficient trafficking of EAAT2-containing vesicles and exocytosis must moreover take place Stenovec et al. Glycogenesis glycogen production from glucose 1-phosphate by glycogen synthase and glycogenolysis glycogen breakdown to glucose 6-phosphate by the combined action of glycogen phosphorylase and phosphoglucomutase mainly occurs in astrocytes Dringen et al. In line with this, glycogen levels were found to increase with anesthesia Morgenthaler et al. However, no change in brain glycogen level was measured during visual stimulation in humans Oz et al. While glycogen-derived lactate has been demonstrated to have a pivotal role in memory formation and consolidation Gibbs and Hertz, ; Suzuki et al. Recently, astrocytic glycogenolysis was shown to provide energy to sustain glutamatergic neurotransmission i. Glycogen might act as a substrate for de novo formation of glutamate Gibbs et al. While the essential role of astrocytes to cerebral function is now widely accepted, quantitative assessment of their actual contribution to energy metabolism has been missing, notably because the methodologies did not allow differentiating between neurons and astrocytes. Direct 13 C MRS along with advanced metabolic modeling can provide measurements of both neuronal and glial metabolism in specific brain regions and under various activation states. In this context, new data indicate that the rate of astrocytic metabolism is about half of that in neurons, and can be activated by sensory stimulation and that the astrocytic response amplitude can be, in absolute terms, as large as in neurons, suggesting that the changes in ATP requirements associated with the glutamate-glutamine cycle are coupled with the ATP produced by glucose oxidation in both compartments. Increase in neuronal metabolism likely supports neurotransmission-associated functions, such as restoration of ion gradients caused by action potentials, post-synaptic currents, and transport of glutamate into vesicles. Adaptation of glial metabolism also provides energy for neurotransmission besides housekeeping tasks, likely fueling the production and action of modulators of neuronal activity and of synaptic plasticity, supply of antioxidant molecules and neurotrophic factors that are necessary for adequate brain function, and regulation of blood flow and volume. Astrocytes are moreover important source of glycogen that can be used specifically for neurotransmission support. Progress in MR detection methods of 1 H and non- 1 H nuclei is a promising direction for more detailed and complete metabolic dataset acquisition. While this provides insights into cellular function in vivo , it also requires improvement of current metabolic models describing best energy metabolism. Simultaneous acquisition of other types of data, such as electrical activity and blood flow, might contribute to more precise characterization of the coupling between brain function and energy metabolism by MRS. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors' research is supported by the Swiss National Science Foundation to JD and to RG ; the National Competence Center in Biomedical Imaging NCCBI ; and by Centre d'Imagerie BioMédicale CIBM of the UNIL, UNIGE, HUG, CHUV, EPFL, and the Leenaards and Jeantet Foundations. Abe, K. The possible role of hydrogen sulfide as an endogenous neuromodulator. PubMed Abstract Google Scholar. Acuña, A. A failure in energy metabolism and antioxidant uptake precede symptoms of Huntington's disease in mice. doi: PubMed Abstract CrossRef Full Text Google Scholar. Almeida, A. Nitric oxide switches on glycolysis through the AMP protein kinase and 6-phosphofructokinase pathway. Cell Biol. Ashrafi, G. GLUT4 mobilization supports energetic demands of active synapses. Neuron 93, — Attwell, D. Glial and neuronal control of brain blood flow. Nature , — An energy budget for signaling in the grey matter of the brain. Blood Flow Metab. Bakken, I. Neuroreport 8, — Barros, L. A quantitative overview of glucose dynamics in the gliovascular unit. Glia 55, — Glucose and lactate supply to the synapse. Brain Res. Bastiaansen, J. Direct noninvasive estimation of myocardial tricarboxylic acid cycle flux in vivo using hyperpolarized 13 C magnetic resonance. Cell Cardiol. CrossRef Full Text Google Scholar. In vivo enzymatic activity of acetylCoA synthetase in skeletal muscle revealed by 13 C turnover from hyperpolarized [1- 13 C]acetate to [1- 13 C]acetylcarnitine. Acta , — Bazargani, N. Astrocyte calcium signaling: the third wave. Bednařík, P. Neurochemical and BOLD responses during neuronal activation measured in the human visual cortex at 7 Tesla. Bergersen, L. Immunogold cytochemistry identifies specialized membrane domains for monocarboxylate transport in the central nervous system. Biesecker, K. Glial cell calcium signalling mediates capillary regulation of blood flow in the retina. Bittner, C. Blood, A. Adenosine mediates decreased cerebral metabolic rate and increased cerebral blood flow during acute moderate hypoxia in the near-term fetal sheep. Bockaert, J. Metabotropic glutamate receptors: an original family of G protein-coupled receptors. Bolaños, J. Glycolysis: a bioenergetic or a survival pathway? Trends Biochem. Borst, P. Mammalian ABC transporters in health and disease. Boury-Jamot, B. Disrupting astrocyte-neuron lactate transfer persistently reduces conditioned responses to cocaine. Psychiatry 21, — Bouzier, A. The metabolism of [3- 13 C]lactate in the rat brain is specific of a pyruvate carboxylase-deprived compartment. Bouzier-Sore, A. Uncertainties in pentose-phosphate pathway flux assessment underestimate its contribution to neuronal glucose consumption: relevance for neurodegeneration and aging. Aging Neurosci. Boveris, A. The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Buerk, D. Temporal dynamics of brain tissue nitric oxide during functional forepaw stimulation in rats. Neuroimage 18, 1—9. Buxton, R. Interpreting oxygenation-based neuroimaging signals: the importance and the challenge of understanding brain oxygen metabolism. Neuroenergetics Cerdan, S. Cerebral metabolism of [1,2- 13 C 2 ]acetate as detected by in vivo and in vitro 13 C NMR. Chaudhry, F. Molecular analysis of system N suggests novel physiological roles in nitrogen metabolism and synaptic transmission. Cell 99, — Glutamine uptake by neurons: interaction of protons with system a transporters. Cheung, G. Connexons and pannexons: newcomers in neurophysiology. Cell Neurosci. Choi, I. Effect of deep pentobarbital anesthesia on neurotransmitter metabolism in vivo : on the correlation of total glucose consumption with glutamatergic action. Comment, A. Dissolution DNP for in vivo preclinical studies. Cornell-Bell, A. The excitatory neurotransmitter glutamate causes filopodia formation in cultured hippocampal astrocytes. Glia 3, — Covarrubias-Pinto, A. Old things new view: ascorbic acid protects the brain in neurodegenerative disorders. Cruz, F. Quantitative 13 C NMR studies of metabolic compartmentation in the adult mammalian brain. NMR Biomed. Ontogeny and cellular localization of the pyruvate recycling system in rat brain. Cruz, N. Activation of astrocytes in brain of conscious rats during acoustic stimulation: acetate utilization in working brain. Deelchand, D. Simultaneous measurement of neuronal and glial metabolism in rat brain in vivo using co-infusion of [1,6- 13 C 2 ]glucose and [1,2- 13 C 2 ]acetate. de Graaf, R. In vivo NMR Spectroscopy: Principles and Techniques. England: Willey. Google Scholar. In vivo 1 H-[ 13 C]-NMR spectroscopy of cerebral metabolism. Regional glucose metabolism and glutamatergic neurotransmission in rat brain in vivo. Dehghani, M. Refined analysis of brain energy metabolism using in vivo dynamic enrichment of 13 C multiplets. ASN Neuro. Denton, R. Regulation of mitochondrial dehydrogenases by calcium ions. Derouiche, A. Astroglial processes around identified glutamatergic synapses contain glutamine synthetase: evidence for transmitter degradation. Fine astrocyte processes contain very small mitochondria: glial oxidative capability may fuel transmitter metabolism. Desagher, S. Astrocytes protect neurons from hydrogen peroxide toxicity. Dienel, G. Brain lactate metabolism: the discoveries and the controversies. A glycogen phosphorylase inhibitor selectively enhances local rates of glucose utilization in brain during sensory stimulation of conscious rats: implications for glycogen turnover. Astrocyte activation in vivo during graded photic stimulation. DiNuzzo, M. Dringen, R. Glutathione pathways in the brain. Synthesis of the antioxidant glutathione in neurons: supply by astrocytes of CysGly as precursor for neuronal glutathione. Incorporation of radioactivity from [ 14 C]lactate into the glycogen of cultured mouse astroglial cells. Evidence for gluconeogenesis in brain cells. Hoppe Seyler , — Duarte, J. Adenosine A 1 receptors control the metabolic recovery after hypoxia in rat hippocampal slices. Brain energy metabolism measured by 13 C magnetic resonance spectroscopy in vivo upon infusion of [3- 13 C]lactate. Glutamatergic and GABAergic energy metabolism measured in the rat brain by 13 C NMR spectroscopy at Compartmentalized Cerebral Metabolism of [1,6- 13 C]Glucose Determined by in vivo 13 C NMR Spectroscopy at The neurochemical profile quantified by in vivo 1 H NMR spectroscopy. Neuroimage 61, — Steady-state brain glucose transport kinetics re-evaluated with a four-state conformational model. Duran, J. Impairment in long-term memory formation and learning-dependent synaptic plasticity in mice lacking glycogen synthase in the brain. El Idrissi, A. Growth factors and taurine protect against excitotoxicity by stabilizing calcium homeostasis and energy metabolism. Erb, L. Coupling of P2Y receptors to G proteins and other signaling pathways. Wiley Interdiscip. Eriksson, G. Sodium-dependent glutamate uptake as an activator of oxidative metabolism in primary astrocyte cultures from newborn rat. Glia 15, — Fresu, L. Plasma membrane calcium ATPase isoforms in astrocytes. Glia 28, — Gamberino, W. Role of pyruvate carboxylase in facilitation of synthesis of glutamate and glutamine in cultured astrocytes. Genda, E. Co-compartmentalization of the astroglial glutamate transporter, GLT-1, with glycolytic enzymes and mitochondria. Ghosh, A. Somatotopic astrocytic activity in the somatosensory cortex. Glia 61, — Gibbs, M. Importance of glutamate-generating metabolic pathways for memory consolidation in chicks. Glycogen is a preferred glutamate precursor during learning in 1-day-old chick: biochemical and behavioral evidence. Goda, Y. SNAREs and regulated vesicle exocytosis. Golgi, C. Sulla Fina Anatomia Degli Organi Centrali del Sistema Nervoso. Milano: Hoepli. Gordon, G. Brain metabolism dictates the polarity of astrocyte control over arterioles. Görlach, A. Calcium and ROS: a mutual interplay. Gruetter, R. In vivo 13 C NMR studies of compartmentalized cerebral carbohydrate metabolism. Localized 13 C NMR spectroscopy in the human brain of amino acid labeling from D-[1- 13 C]glucose. Localized in vivo 13 C-NMR of glutamate metabolism in the human brain: initial results at 4 tesla. A mathematical model of compartmentalized neurotransmitter metabolism in the human brain. Steady-state cerebral glucose concentrations and transport in the human brain. Haberg, A. In vivo effects of adenosine A 1 receptor agonist and antagonist on neuronal and astrocytic intermediary metabolism studied with ex vivo 13 C NMR spectroscopy. Hajek, I. Halassa, M. Synaptic islands defined by the territory of a single astrocyte. Hamilton, N. Pericyte-mediated regulation of capillary diameter: a component of neurovascular coupling in health and disease. Hammer, J. In vivo effects of adenosine A 2 receptor agonist and antagonist on neuronal and astrocytic intermediary metabolism studied with ex vivo 13 C MR spectroscopy. Hancu, I. The case of the missing glutamine. Henry, P. In vivo 13 C NMR spectroscopy and metabolic modeling in the brain: a practical perspective. Imaging 24, — Decreased TCA cycle rate in the rat brain after acute 3-NP treatment measured by in vivo 1 H-[ 13 C] NMR spectroscopy. Herrero-Mendez, A. Hertz, L. Energy metabolism in the brain. Astrocytic glycogenolysis: mechanisms and functions. Brain Dis. Honegger, P. Howarth, C. A critical role for astrocytes in hypercapnic vasodilation in brain. Hyder, F. Increased tricarboxylic acid cycle flux in rat brain during forepaw stimulation detected with 1 H[ 13 C]NMR. Oxidative glucose metabolism in rat brain during single forepaw stimulation: a spatially localized 1 H[ 13 C] nuclear magnetic resonance study. Flow Metab. Iadecola, C. Neurovascular regulation in the normal brain and in Alzheimer's disease. Glial regulation of the cerebral microvasculature. Ido, Y. NADH: sensor of blood flow need in brain, muscle, and other tissues. FASEB J. Ikebuchi, Y. Superoxide anion increases intracellular pH, intracellular free calcium, and arachidonate release in human amnion cells. Iliff, J. Adenosine receptors mediate glutamate-evoked arteriolar dilation in the rat cerebral cortex. Jackson, J. Neuronal activity and glutamate uptake decrease mitochondrial mobility in astrocytes and position mitochondria near glutamate transporters. Reciprocal regulation of mitochondrial dynamics and calcium signaling in astrocyte processes. Jackson, P. The volume-sensitive organic osmolyte-anion channel VSOAC is regulated by nonhydrolytic ATP binding. Jimenez-Blasco, D. Astrocyte NMDA receptors' activity sustains neuronal survival through a Cdk5-Nrf2 pathway. Cell Death Differ. Joseph, S. Colocalization of ATP release sites and ecto-ATPase activity at the extracellular surface of human astrocytes. Just, N. Characterization of sustained BOLD activation in the rat barrel cortex and neurochemical consequences. Neuroimage 74, — Kacem, K. Structural organization of the perivascular astrocyte endfeet and their relationship with the endothelial glucose transporter: a confocal microscopy study. Glia 23, 1— Karaca, M. GDH-dependent glutamate oxidation in the brain dictates peripheral energy substrate distribution. Cell Rep. Kasischke, K. Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis. Science , 99— Kettenmann, H. Neuroglia: the years after. Trends Neurosci. Koehler, R. Role of astrocytes in cerebrovascular regulation. Korn, E. Actin polymerization and ATP hydrolysis. Science , — Kuge, Y. Brain uptake and metabolism of [1- 11 C]octanoate in rats: pharmacokinetic basis for its application as a radiopharmaceutical for studying brain fatty acid metabolism. Künnecke, B. Cerebral metabolism of [1,2- 13 C 2 ]glucose and [UC4]3-hydroxybutyrate in rat brain as detected by 13 C NMR spectroscopy. Kuschinsky, W. Local chemical and neurogenic regulation of cerebral vascular resistance. Lanz, B. Metabolic flux and compartmentation analysis in the brain in vivo. In vivo quantification of neuro-glial metabolism and glial glutamate concentration using 1 H-[ 13 C] MRS at Laranjinha, J. Nitric oxide signaling in the brain: translation of dynamics into respiration control and neurovascular coupling. Lebon, V. Astroglial contribution to brain energy metabolism in humans revealed by 13 C nuclear magnetic resonance spectroscopy: elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism. Le Clainche, C. Lee, M. Astrocytes produce the antiinflammatory and neuroprotective agent hydrogen sulfide. Aging 30, — Lee, W. Glutamine transport by the blood-brain barrier: a possible mechanism for nitrogen removal. Lerchundi, R. Li, S. Lin, A. Time-dependent correlation of cerebral blood flow with oxygen metabolism in activated human visual cortex as measured by fMRI. Neuroimage 44, 16— Lin, Y. Investigating the metabolic changes due to visual stimulation using functional proton magnetic resonance spectroscopy at 7 T. Lind, B. Lourenço, C. Neurovascular coupling in hippocampus is mediated via diffusion by neuronal-derived nitric oxide. Free Radic. Lovatt, D. The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex. Lundgaard, I. Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism. Mächler, P. In vivo evidence for a lactate gradient from astrocytes to neurons. Cell Metab. Maher, F. Substrate specificity and kinetic parameters of GLUT3 in rat cerebellar granule neurons. Glucose transporter proteins in brain. Expression of mouse-GLUT3 and human-GLUT3 glucose transporter proteins in brain. Makar, T. Vitamin, E. Mangia, S. Sustained neuronal activation raises oxidative metabolism to a new steady-state level: evidence from 1 H NMR spectroscopy in the human visual cortex. Masamoto, K. Anesthesia and the quantitative evaluation of neurovascular coupling. Mason, G. Mathiisen, T. The perivascular astroglial sheath provides a complete covering of the brain microvessels: an electron microscopic 3D reconstruction. Glia 58, — McIlwain, H. Electrical stimulation in vitro of the metabolism of glucose by mammalian cerebral cortex. McKenna, M. The glutamate-glutamine cycle is not stoichiometric: fates of glutamate in brain. Glutamate pays its own way in astrocytes. Lausanne Exogenous glutamate concentration regulates the metabolic fate of glutamate in astrocytes. Metea, M. Glial cells dilate and constrict blood vessels: a mechanism of neurovascular coupling. Mishkovsky, M. In vivo detection of brain Krebs cycle intermediate by hyperpolarized magnetic resonance. Morgenthaler, F. Biochemical quantification of total brain glycogen concentration in rats under different glycemic states. Nagai, Y. Hydrogen sulfide induces calcium waves in astrocytes. Nedergaard, M. 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Close Navbar Search Filter Oxford Academic Functional Magnetic Resonance Imaging: An Introduction to Methods Neuroscientific Techniques Oxford Scholarship Online Books Journals Enter search term Search. Advanced Search. Search Menu. Close navigation menu Functional Magnetic Resonance Imaging: An Introduction to Methods Peter Jezzard ed. et al. Search in this book. Expand Front Matter. Expand I Introduction. Collapse II Physics and physiology. Collapse 2 Brain energy metabolism and the physiological basis of the haemodynamic response. Expand 2. Glucose transport for glycolysis Glucose transport for glycolysis. Controlling the rate of glycolysis: hexokinase and phosphofructokinase Controlling the rate of glycolysis: hexokinase and phosphofructokinase. Pyruvate and lactate production link glycolysis to oxidative metabolism Pyruvate and lactate production link glycolysis to oxidative metabolism. Transport of pyruvate and lactate out of cells Transport of pyruvate and lactate out of cells. Mitochondrial dehydrogenases and control of the tricarboxylic acid cycle Mitochondrial dehydrogenases and control of the tricarboxylic acid cycle. Cytochrome oxidase and control of the electron transport chain Cytochrome oxidase and control of the electron transport chain. Modulation of substrate flux for oxidative phosporylation by calcium Modulation of substrate flux for oxidative phosporylation by calcium. Coupling of energy metabolism to glutamate transport Coupling of energy metabolism to glutamate transport. Joint contribution of neurones and astrocytes to increased brain glucose utilization accompanying increased brain activity Joint contribution of neurones and astrocytes to increased brain glucose utilization accompanying increased brain activity. |
| Dementia: Poor metabolism linked to poor brain health | Race and Ethnicity. In contrast, long-term facilitation of motor output in adult rats is enhanced by intermittent hypoxia 3 × 3 min intervals, separated by 5 min hyperoxia increasing both phrenic amplitude and burst frequency, which was not observed with a continuous hypoxia of the same cumulative duration Baker and Mitchell, Naval Forces and Warfare. Iron and zinc homeostases in female rats with physically active and sedentary lifestyles. Paolinelli R, Corada M, Ferrarini L, Devraj K, Artus C, Czupalla CJ, et al. Article CAS PubMed PubMed Central Google Scholar Zhao N, Zhang X, Li B, Wang J, Zhang C, Xu B. |
| Energy Metabolism and Brain Functions - Harvard Brain Science Initiative | BDNF mediates adaptive brain and body responses to energetic challenges. All the processes described in this textbook require energy. Writing Systems. For example, mitochondria play a critical role in the production and regulation of neurotransmitters, such as serotonin, dopamine , and GABA. Engineering General. Article PubMed PubMed Central Google Scholar Strohle A, Schmidt DK, Schultz F, Fricke N, Staden T, Hellweg R, et al. |
| Latest news | Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, Alberini CM Astrocyte-neuron lactate transport is required for long-term memory formation. Cell 5 — Download references. Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne EPFL , , Lausanne, Switzerland. Pierre J. Igor Allaman. Department of Psychiatry—CHUV, Center for Psychiatric Neuroscience, , Prilly—Lausanne, Switzerland. You can also search for this author in PubMed Google Scholar. Correspondence to Pierre J. Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY, USA. Reprints and permissions. Magistretti, P. In: Pfaff, D. eds Neuroscience in the 21st Century. Springer, New York, NY. Publisher Name : Springer, New York, NY. Print ISBN : Online ISBN : eBook Packages : Biomedical and Life Sciences Reference Module Biomedical and Life Sciences. Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Policies and ethics. Skip to main content. Abstract All the processes described in this textbook require energy. Keywords Positron Emission Tomography Pentose Phosphate Pathway Glucose Utilization Ketone Body Energy Substrate These keywords were added by machine and not by the authors. Buying options Chapter EUR eBook EUR 1, Tax calculation will be finalised at checkout Purchases are for personal use only Learn about institutional subscriptions. Further Reading Bélanger M, Allaman I, Magistretti PJ Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab — Article PubMed Google Scholar Figley CR, Stroman PW The role s of astrocytes and astrocyte activity in neurometabolism, neurovascular coupling, and the production of functional neuroimaging signals. Eur J Neurosci — Article PubMed Google Scholar Frackowiak RSJ, Magistretti PJ, Shulman RG, Adams M Neuroenergetics: relevance for functional brain imaging. Ashrafi, G. GLUT4 mobilization supports energetic demands of active synapses. Neuron 93, — Attwell, D. Glial and neuronal control of brain blood flow. Nature , — An energy budget for signaling in the grey matter of the brain. Blood Flow Metab. Bakken, I. Neuroreport 8, — Barros, L. A quantitative overview of glucose dynamics in the gliovascular unit. Glia 55, — Glucose and lactate supply to the synapse. Brain Res. Bastiaansen, J. Direct noninvasive estimation of myocardial tricarboxylic acid cycle flux in vivo using hyperpolarized 13 C magnetic resonance. Cell Cardiol. CrossRef Full Text Google Scholar. In vivo enzymatic activity of acetylCoA synthetase in skeletal muscle revealed by 13 C turnover from hyperpolarized [1- 13 C]acetate to [1- 13 C]acetylcarnitine. Acta , — Bazargani, N. Astrocyte calcium signaling: the third wave. Bednařík, P. Neurochemical and BOLD responses during neuronal activation measured in the human visual cortex at 7 Tesla. Bergersen, L. Immunogold cytochemistry identifies specialized membrane domains for monocarboxylate transport in the central nervous system. Biesecker, K. Glial cell calcium signalling mediates capillary regulation of blood flow in the retina. Bittner, C. Blood, A. Adenosine mediates decreased cerebral metabolic rate and increased cerebral blood flow during acute moderate hypoxia in the near-term fetal sheep. Bockaert, J. Metabotropic glutamate receptors: an original family of G protein-coupled receptors. Bolaños, J. Glycolysis: a bioenergetic or a survival pathway? Trends Biochem. Borst, P. Mammalian ABC transporters in health and disease. Boury-Jamot, B. Disrupting astrocyte-neuron lactate transfer persistently reduces conditioned responses to cocaine. Psychiatry 21, — Bouzier, A. The metabolism of [3- 13 C]lactate in the rat brain is specific of a pyruvate carboxylase-deprived compartment. Bouzier-Sore, A. Uncertainties in pentose-phosphate pathway flux assessment underestimate its contribution to neuronal glucose consumption: relevance for neurodegeneration and aging. Aging Neurosci. Boveris, A. The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Buerk, D. Temporal dynamics of brain tissue nitric oxide during functional forepaw stimulation in rats. Neuroimage 18, 1—9. Buxton, R. Interpreting oxygenation-based neuroimaging signals: the importance and the challenge of understanding brain oxygen metabolism. Neuroenergetics Cerdan, S. Cerebral metabolism of [1,2- 13 C 2 ]acetate as detected by in vivo and in vitro 13 C NMR. Chaudhry, F. Molecular analysis of system N suggests novel physiological roles in nitrogen metabolism and synaptic transmission. Cell 99, — Glutamine uptake by neurons: interaction of protons with system a transporters. Cheung, G. Connexons and pannexons: newcomers in neurophysiology. Cell Neurosci. Choi, I. Effect of deep pentobarbital anesthesia on neurotransmitter metabolism in vivo : on the correlation of total glucose consumption with glutamatergic action. Comment, A. Dissolution DNP for in vivo preclinical studies. Cornell-Bell, A. The excitatory neurotransmitter glutamate causes filopodia formation in cultured hippocampal astrocytes. Glia 3, — Covarrubias-Pinto, A. Old things new view: ascorbic acid protects the brain in neurodegenerative disorders. Cruz, F. Quantitative 13 C NMR studies of metabolic compartmentation in the adult mammalian brain. NMR Biomed. Ontogeny and cellular localization of the pyruvate recycling system in rat brain. Cruz, N. Activation of astrocytes in brain of conscious rats during acoustic stimulation: acetate utilization in working brain. Deelchand, D. Simultaneous measurement of neuronal and glial metabolism in rat brain in vivo using co-infusion of [1,6- 13 C 2 ]glucose and [1,2- 13 C 2 ]acetate. de Graaf, R. In vivo NMR Spectroscopy: Principles and Techniques. England: Willey. Google Scholar. In vivo 1 H-[ 13 C]-NMR spectroscopy of cerebral metabolism. Regional glucose metabolism and glutamatergic neurotransmission in rat brain in vivo. Dehghani, M. Refined analysis of brain energy metabolism using in vivo dynamic enrichment of 13 C multiplets. ASN Neuro. Denton, R. Regulation of mitochondrial dehydrogenases by calcium ions. Derouiche, A. Astroglial processes around identified glutamatergic synapses contain glutamine synthetase: evidence for transmitter degradation. Fine astrocyte processes contain very small mitochondria: glial oxidative capability may fuel transmitter metabolism. Desagher, S. Astrocytes protect neurons from hydrogen peroxide toxicity. Dienel, G. Brain lactate metabolism: the discoveries and the controversies. A glycogen phosphorylase inhibitor selectively enhances local rates of glucose utilization in brain during sensory stimulation of conscious rats: implications for glycogen turnover. Astrocyte activation in vivo during graded photic stimulation. DiNuzzo, M. Dringen, R. Glutathione pathways in the brain. Synthesis of the antioxidant glutathione in neurons: supply by astrocytes of CysGly as precursor for neuronal glutathione. Incorporation of radioactivity from [ 14 C]lactate into the glycogen of cultured mouse astroglial cells. Evidence for gluconeogenesis in brain cells. Hoppe Seyler , — Duarte, J. Adenosine A 1 receptors control the metabolic recovery after hypoxia in rat hippocampal slices. Brain energy metabolism measured by 13 C magnetic resonance spectroscopy in vivo upon infusion of [3- 13 C]lactate. Glutamatergic and GABAergic energy metabolism measured in the rat brain by 13 C NMR spectroscopy at Compartmentalized Cerebral Metabolism of [1,6- 13 C]Glucose Determined by in vivo 13 C NMR Spectroscopy at The neurochemical profile quantified by in vivo 1 H NMR spectroscopy. Neuroimage 61, — Steady-state brain glucose transport kinetics re-evaluated with a four-state conformational model. Duran, J. Impairment in long-term memory formation and learning-dependent synaptic plasticity in mice lacking glycogen synthase in the brain. El Idrissi, A. Growth factors and taurine protect against excitotoxicity by stabilizing calcium homeostasis and energy metabolism. Erb, L. Coupling of P2Y receptors to G proteins and other signaling pathways. Wiley Interdiscip. Eriksson, G. Sodium-dependent glutamate uptake as an activator of oxidative metabolism in primary astrocyte cultures from newborn rat. Glia 15, — Fresu, L. Plasma membrane calcium ATPase isoforms in astrocytes. Glia 28, — Gamberino, W. Role of pyruvate carboxylase in facilitation of synthesis of glutamate and glutamine in cultured astrocytes. Genda, E. Co-compartmentalization of the astroglial glutamate transporter, GLT-1, with glycolytic enzymes and mitochondria. Ghosh, A. Somatotopic astrocytic activity in the somatosensory cortex. Glia 61, — Gibbs, M. Importance of glutamate-generating metabolic pathways for memory consolidation in chicks. Glycogen is a preferred glutamate precursor during learning in 1-day-old chick: biochemical and behavioral evidence. Goda, Y. SNAREs and regulated vesicle exocytosis. Golgi, C. Sulla Fina Anatomia Degli Organi Centrali del Sistema Nervoso. Milano: Hoepli. Gordon, G. Brain metabolism dictates the polarity of astrocyte control over arterioles. Görlach, A. Calcium and ROS: a mutual interplay. Gruetter, R. In vivo 13 C NMR studies of compartmentalized cerebral carbohydrate metabolism. Localized 13 C NMR spectroscopy in the human brain of amino acid labeling from D-[1- 13 C]glucose. Localized in vivo 13 C-NMR of glutamate metabolism in the human brain: initial results at 4 tesla. A mathematical model of compartmentalized neurotransmitter metabolism in the human brain. Steady-state cerebral glucose concentrations and transport in the human brain. Haberg, A. In vivo effects of adenosine A 1 receptor agonist and antagonist on neuronal and astrocytic intermediary metabolism studied with ex vivo 13 C NMR spectroscopy. Hajek, I. Halassa, M. Synaptic islands defined by the territory of a single astrocyte. Hamilton, N. Pericyte-mediated regulation of capillary diameter: a component of neurovascular coupling in health and disease. Hammer, J. In vivo effects of adenosine A 2 receptor agonist and antagonist on neuronal and astrocytic intermediary metabolism studied with ex vivo 13 C MR spectroscopy. Hancu, I. The case of the missing glutamine. Henry, P. In vivo 13 C NMR spectroscopy and metabolic modeling in the brain: a practical perspective. Imaging 24, — Decreased TCA cycle rate in the rat brain after acute 3-NP treatment measured by in vivo 1 H-[ 13 C] NMR spectroscopy. Herrero-Mendez, A. Hertz, L. Energy metabolism in the brain. Astrocytic glycogenolysis: mechanisms and functions. Brain Dis. Honegger, P. Howarth, C. A critical role for astrocytes in hypercapnic vasodilation in brain. Hyder, F. Increased tricarboxylic acid cycle flux in rat brain during forepaw stimulation detected with 1 H[ 13 C]NMR. Oxidative glucose metabolism in rat brain during single forepaw stimulation: a spatially localized 1 H[ 13 C] nuclear magnetic resonance study. Flow Metab. Iadecola, C. Neurovascular regulation in the normal brain and in Alzheimer's disease. Glial regulation of the cerebral microvasculature. Ido, Y. NADH: sensor of blood flow need in brain, muscle, and other tissues. FASEB J. Ikebuchi, Y. Superoxide anion increases intracellular pH, intracellular free calcium, and arachidonate release in human amnion cells. Iliff, J. Adenosine receptors mediate glutamate-evoked arteriolar dilation in the rat cerebral cortex. Jackson, J. Neuronal activity and glutamate uptake decrease mitochondrial mobility in astrocytes and position mitochondria near glutamate transporters. Reciprocal regulation of mitochondrial dynamics and calcium signaling in astrocyte processes. Jackson, P. The volume-sensitive organic osmolyte-anion channel VSOAC is regulated by nonhydrolytic ATP binding. Jimenez-Blasco, D. Astrocyte NMDA receptors' activity sustains neuronal survival through a Cdk5-Nrf2 pathway. Cell Death Differ. Joseph, S. Colocalization of ATP release sites and ecto-ATPase activity at the extracellular surface of human astrocytes. Just, N. Characterization of sustained BOLD activation in the rat barrel cortex and neurochemical consequences. Neuroimage 74, — Kacem, K. Structural organization of the perivascular astrocyte endfeet and their relationship with the endothelial glucose transporter: a confocal microscopy study. Glia 23, 1— Karaca, M. GDH-dependent glutamate oxidation in the brain dictates peripheral energy substrate distribution. Cell Rep. Kasischke, K. Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis. Science , 99— Kettenmann, H. Neuroglia: the years after. Trends Neurosci. Koehler, R. Role of astrocytes in cerebrovascular regulation. Korn, E. Actin polymerization and ATP hydrolysis. Science , — Kuge, Y. Brain uptake and metabolism of [1- 11 C]octanoate in rats: pharmacokinetic basis for its application as a radiopharmaceutical for studying brain fatty acid metabolism. Künnecke, B. Cerebral metabolism of [1,2- 13 C 2 ]glucose and [UC4]3-hydroxybutyrate in rat brain as detected by 13 C NMR spectroscopy. Kuschinsky, W. Local chemical and neurogenic regulation of cerebral vascular resistance. Lanz, B. Metabolic flux and compartmentation analysis in the brain in vivo. In vivo quantification of neuro-glial metabolism and glial glutamate concentration using 1 H-[ 13 C] MRS at Laranjinha, J. Nitric oxide signaling in the brain: translation of dynamics into respiration control and neurovascular coupling. Lebon, V. Astroglial contribution to brain energy metabolism in humans revealed by 13 C nuclear magnetic resonance spectroscopy: elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism. Le Clainche, C. Lee, M. Astrocytes produce the antiinflammatory and neuroprotective agent hydrogen sulfide. Aging 30, — Lee, W. Glutamine transport by the blood-brain barrier: a possible mechanism for nitrogen removal. Lerchundi, R. Li, S. Lin, A. Time-dependent correlation of cerebral blood flow with oxygen metabolism in activated human visual cortex as measured by fMRI. Neuroimage 44, 16— Lin, Y. Investigating the metabolic changes due to visual stimulation using functional proton magnetic resonance spectroscopy at 7 T. Lind, B. Lourenço, C. Neurovascular coupling in hippocampus is mediated via diffusion by neuronal-derived nitric oxide. Free Radic. Lovatt, D. The transcriptome and metabolic gene signature of protoplasmic astrocytes in the adult murine cortex. Lundgaard, I. Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism. Mächler, P. In vivo evidence for a lactate gradient from astrocytes to neurons. Cell Metab. Maher, F. Substrate specificity and kinetic parameters of GLUT3 in rat cerebellar granule neurons. Glucose transporter proteins in brain. Expression of mouse-GLUT3 and human-GLUT3 glucose transporter proteins in brain. The highlighted cortical regions above are the nodes of a large-scale brain network. These areas usually show synchronized neural activity or in other words, functional connectivity FC , as they work towards a common goal. In this study, a positive correlation was found between the strength of this synchronization or connectivity and the rate of the creatine kinase reaction, which would be critical for orchestrating oscillatory states, and enhancing the fidelity of information processing for better executive and cognitive function. Xiaopeng Song is a postdoctoral fellow in the lab of Dr. Fei Du at McLean Hospital, Harvard Medical School. Learn more in the original research article: Bioenergetics and abnormal functional connectivity in psychotic disorders. Song X, Chen X, Yuksel C, Yuan J, Pizzagalli DA, Forester B, Öngür D, Du F. Mol Psychiatry. doi: |
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