The Metabolism of [3‐<sup>13</sup>C]Lactate in the Rat Brain Is Specific of a Pyruvate Carboxylase‐Deprived Compartment

Bouzier, Anne-Karine; Thiaudière, Eric; Biran, Marc; Rouland, Richard; Canioni, Paul; Merle, M.

doi:10.1046/j.1471-4159.2000.0750480.x

Cited by 97 publications

(147 citation statements)

References 38 publications

(45 reference statements)

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“…As shown previously, infusing both substrates made it possible to reach higher blood concentrations than after the infusion of only one of them and minimized the consequences of hepatic gluconeogenesis on their labeling (8). After a 20-min infusion, glucose concentration was slightly lower under ␣-chloralose than under pentobarbital or morphine anesthesia, whereas lactate concentration was ϳ2-fold higher under morphine than under pentobarbital or ␣-chloralose (Table I).…”

Section: Concentration and Specific Enrichment Of Glucose Lactate Asupporting

confidence: 52%

“…The infusion flow was monitored to follow a time-decreasing exponential as described previously (8). A few minutes before the end of infusion, a longitudinal incision was made on the scalp of the animals, and its two parts were drawn aside to make the cranium apparent.…”

Section: Methodsmentioning

confidence: 99%

“…1 H-observed/ 13 C-edited spectra were obtained as described previously (8). The acquisition sequences involved a proton spin echo with calibrated 90 and 180°pulses separated by a 3.94-ms delay corresponding to the 0.5 J CH value for the 1 H-13 C scalar coupling in amino acid -CH 2 -and -CH 3 (J CH ϭ 126 -132 Hz) either with or without 13 C spin inversion with a 90, 120, 120, and 90°composite pulse (8.75 s for 90°flip angle).…”

Section: Methodsmentioning

confidence: 99%

“…The presence of [3-13 C]lactate in the blood with the infusion of [1-13 C]glucose plus lactate resulted from glycolysis, and that of labeled glucose with the infusion of glucose plus [3-13 C]lactate resulted from hepatic gluconeogenesis, the activity of which led to the labeling of glucose carbons at the different positions (with the same labeling level at C1, C2, C5, and C6) (8). Glycolytic activity was higher under morphine than under pentobarbital or ␣-chloralose, as revealed both by the lower and higher lactate enrichment with glucose plus [3-13 C]lactate and [1-…”

Section: Glucose and Lactate Concentrations And Enrichments In Blood Andmentioning

confidence: 99%

“…Time dependence of lactate C3 and alanine C3 enrichments in rat brain after blood circulation arrest. The rats treated with either pentobarbital (A), ␣-chloralose (B), or morphine (C) were infused with a solution of 750 mM [1][2][3][4][5][6][7][8][9][10][11][12][13] C]glucose plus 500 mM lactate. Time zero was defined as the instant when their cranium was split in two parts to remove brain hemispheres.…”

Section: Involvement Of Brain Lactate In the Neuronal Metabolism-mentioning

confidence: 99%

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Ex Vivo Analysis of Lactate and Glucose Metabolism in the Rat Brain under Different States of Depressed Activity

Serres

Bezancon

Franconi

et al. 2004

Journal of Biological Chemistry

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Brain metabolism of glucose and lactate was analyzed by ex vivo NMR spectroscopy in rats presenting different cerebral activities induced after the administration of pentobarbital, ␣-chloralose, or morphine. The animals were infused with a solution of either [1-13 C]glucose plus lactate or glucose plus [3-13 C]lactate for 20 min. Brain metabolite contents and enrichments were determined from analyses of brain tissue perchloric acid extracts according to their post-mortem evolution kinetics. When amino acid enrichments were compared, both the brain metabolic activity and the contribution of blood glucose relative to that of blood lactate to brain metabolism were linked with cerebral activity. The data also indicated the production in the brain of lactate from glycolysis in a compartment other than the neurons, presumably the astrocytes, and its subsequent oxidative metabolism in neurons. Therefore, a brain electrical activity-dependent increase in the relative contribution of blood glucose to brain metabolism occurred via the increase in the metabolism of lactate generated from brain glycolysis at the expense of that of blood lactate. This result strengthens the hypothesis that brain lactate is involved in the coupling between neuronal activation and metabolism.In the last decade, the idea of the involvement of lactate in the coupling between neuronal activation and energy metabolism has arisen from the results of various experimental investigations. Briefly, in vitro studies have evidenced lactate release from astrocytes after glycolysis stimulation by glutamate uptake (1, 2) and, in the particular case of the mammalian retina, the use of lactate from Mü ller cells as an energy substrate for photoreceptors (3). In vivo studies on brain have demonstrated the uncoupling of oxygen and glucose utilization (4) and the release of lactate into the extracellular fluid in response to neuronal activation (5, 6). On the other hand, brain lactate has been demonstrated to efficiently protect neurons against delayed ischemic damage (7). The metabolic fate of exogenous lactate in whole brain has been investigated by ex vivo NMR spectroscopy. In this way, it has been demonstrated that blood lactate enters the brain and is more specifically metabolized in neurons (8 -10). The proposed astrocyte-neuron lactate shuttle hypothesis (ANLSH) 1 (1) as the coupling model between neuronal activity and energy metabolism requires the involvement of different components, the occurrence and localization of which have been investigated analytically at the molecular level, i.e. glutamate transporter and Na ϩ ,K ϩ -ATPase (11), lactate dehydrogenase isoenzymes (12), and monocarboxylate transporters (13,14). Although brain lactate production and lactate use by neurons as an energy source are widely admitted, the relevance of the coupling model, particularly the neuronal utilization of glia-produced lactate, is a topical issue (15, 16).Brain lactate mostly derives from glycolysis. Therefore, the comparative analysis of the contribution of brain l...

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Section: Concentration and Specific Enrichment Of Glucose Lactate Asupporting

confidence: 52%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Glucose and Lactate Concentrations And Enrichments In Blood Andmentioning

confidence: 99%

Section: Involvement Of Brain Lactate In the Neuronal Metabolism-mentioning

confidence: 99%

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Ex Vivo Analysis of Lactate and Glucose Metabolism in the Rat Brain under Different States of Depressed Activity

Serres

Bezancon

Franconi

et al. 2004

Journal of Biological Chemistry

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Radial glia express aromatase in the injured zebra finch brain

Peterson

Lee

Fernando

et al. 2004

J of Comparative Neurology

101

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Estrogens have neurotrophic and neuroprotective properties. The synthesis of estrogen occurs via the expression of aromatase. Previous studies have shown that injury to the vertebrate brain results in a rapid and dramatic up-regulation of aromatase expression in astrocytes around the lesion. As part of experiments examining injury-induced glial aromatization, we identified aromatase in radial glia of the zebra finch brain. Adult female zebra finches received a penetrating injury to the right hippocampus. Twenty-four hours after lesioning, birds were administered bromodeoxyuridine (BrdU) and sacrificed 2 hours, 1 day, or 7 days later. We determined the distribution of aromatase and BrdU labeling by using immunocytochemistry. Radial aromatase was localized to cells lining the lateral ventricle adjacent to the lesioned hippocampus. Injury also induced a dramatic accumulation of newly generated cells labeled with BrdU around the lesion. BrdU labeling was strongly associated with aromatase-positive radial fibers, suggesting the migration of newly generated cells along these fibers. In the songbird brain, estrogen supports neuronal recruitment and promotes the survival and addition of new neurons. The presence of aromatase in radial glia provides a mechanism of estrogen delivery to postmitotic cells. Radial aromatization may be a key feature in the repair of the vertebrate brain following neural injury.

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¹³C isotopomer analysis of glucose and alanine metabolism reveals cytosolic pyruvate compartmentation as part of energy metabolism in astrocytes

Zwingmann

Richter‐Landsberg

Leibfritz

2001

Glia

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After incubation of glial cells with both (13)C-labeled and unlabeled glucose and alanine, (13)C isotopomer analysis indicates two cytosolic pyruvate compartments in astrocytes. One pyruvate pool is in an exchange equilibrium with exogenous alanine and preferentially synthesizes releasable lactate. The second pyruvate pool, which is of glycolytic origin, is more closely related to mitochondrial pyruvate, which is oxidized via tri carbonic acid (TCA) cycle activity. In order to provide 2-oxoglutarate as a substrate for cytosolic alanine aminotransferase, glycolytic activity is increased in the presence of exogenous alanine. Furthermore, in the presence of alanine, glutamate is accumulated in astrocytes without subsequent glutamine synthesis. We suggest that the conversion of alanine to releasable lactate proceeds at the expense of flux of glycolytic pyruvate through lactate dehydrogenase, which is used for ammonia fixation by alanine synthesis in the cytosol and for mitochondrial TCA cycle activity. In addition, an intracellular trafficking occurs between cytosol and mitochondria, by which these two cytosolic pyruvate pools are partly connected. Thus, exogenous alanine modifies astrocytic glucose metabolism for the synthesis of releasable lactate disconnected from glycolysis. The data are discussed in terms of astrocytic energy metabolism and the metabolic trafficking via a putative alanine-lactate shuttle between astrocytes and neurons.

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The Metabolism of [3‐¹³C]Lactate in the Rat Brain Is Specific of a Pyruvate Carboxylase‐Deprived Compartment

Cited by 97 publications

References 38 publications

Ex Vivo Analysis of Lactate and Glucose Metabolism in the Rat Brain under Different States of Depressed Activity

Ex Vivo Analysis of Lactate and Glucose Metabolism in the Rat Brain under Different States of Depressed Activity

Radial glia express aromatase in the injured zebra finch brain

¹³C isotopomer analysis of glucose and alanine metabolism reveals cytosolic pyruvate compartmentation as part of energy metabolism in astrocytes

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The Metabolism of [3‐13C]Lactate in the Rat Brain Is Specific of a Pyruvate Carboxylase‐Deprived Compartment

Cited by 97 publications

References 38 publications

Ex Vivo Analysis of Lactate and Glucose Metabolism in the Rat Brain under Different States of Depressed Activity

Ex Vivo Analysis of Lactate and Glucose Metabolism in the Rat Brain under Different States of Depressed Activity

Radial glia express aromatase in the injured zebra finch brain

13C isotopomer analysis of glucose and alanine metabolism reveals cytosolic pyruvate compartmentation as part of energy metabolism in astrocytes

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Resources

About

The Metabolism of [3‐¹³C]Lactate in the Rat Brain Is Specific of a Pyruvate Carboxylase‐Deprived Compartment

¹³C isotopomer analysis of glucose and alanine metabolism reveals cytosolic pyruvate compartmentation as part of energy metabolism in astrocytes