scholarly journals A Subconvulsive Dose of Kainate Selectively Compromises Astrocytic Metabolism in the Mouse Brain In Vivo

2014 ◽  
Vol 34 (8) ◽  
pp. 1340-1346 ◽  
Author(s):  
Anne B Walls ◽  
Elvar M Eyjolfsson ◽  
Arne Schousboe ◽  
Ursula Sonnewald ◽  
Helle S Waagepetersen
Keyword(s):  
Seizure Activity ◽  
Cerebral Metabolism ◽  
Tca Cycle ◽  
Resonance Spectroscopy ◽  
Neuronal Function ◽  
Limbic Seizures ◽  
Adult Mice ◽  
Neuronal Metabolism ◽  
Instantaneous Increase

Despite the well-established use of kainate as a model for seizure activity and temporal lobe epilepsy, most studies have been performed at doses giving rise to general limbic seizures and have mainly focused on neuronal function. Little is known about the effect of lower doses of kainate on cerebral metabolism and particularly that associated with astrocytes. We investigated astrocytic and neuronal metabolism in the cerebral cortex of adult mice after treatment with saline (controls), a subconvulsive or a mildly convulsive dose of kainate. A combination of [1,2-13C]acetate and [1-13C]glucose was injected and subsequent nuclear magnetic resonance spectroscopy of cortical extracts was employed to distinctively map astrocytic and neuronal metabolism. The subconvulsive dose of kainate led to an instantaneous increase in the cortical lactate content, a subsequent reduction in the amount of [4,5-13C]glutamine and an increase in the calculated astrocytic TCA cycle activity. In contrast, the convulsive dose led to decrements in the cortical content and 13C labeling of glutamate, glutamine, GABA, and aspartate. Evidence is provided that astrocytic metabolism is affected by a subconvulsive dose of kainate, whereas a higher dose is required to affect neuronal metabolism. The cerebral glycogen content was dose-dependently reduced by kainate supporting a role for glycogen during seizure activity.

scholarly journals Assessment of Metabolic Fluxes in the Mouse Brain in Vivo Using 1H-[13C] NMR Spectroscopy at 14.1 Tesla

2015 ◽  
Vol 35 (5) ◽  
pp. 759-765 ◽  
Author(s):  
Lijing Xin ◽  
Bernard Lanz ◽  
gxia Lei ◽  
Rolf Gruetter
Keyword(s):  
Mouse Models ◽  
Mouse Brain ◽  
Conversion Rate ◽  
Tca Cycle ◽  
Compartment Model ◽  
13C Nmr Spectroscopy ◽  
Resonance Spectroscopy ◽  
Metabolic Fluxes ◽  
Short Echo Time

13C magnetic resonance spectroscopy (MRS) combined with the administration of 13C labeled substrates uniquely allows to measure metabolic fluxes in vivo in the brain of humans and rats. The extension to mouse models may provide exclusive prospect for the investigation of models of human diseases. In the present study, the short-echo-time (TE) full-sensitivity 1H-[13C] MRS sequence combined with high magnetic field (14.1 T) and infusion of [U-13C6] glucose was used to enhance the experimental sensitivity in vivo in the mouse brain and the 13C turnover curves of glutamate C4, glutamine C4, glutamate+glutamine C3, aspartate C2, lactate C3, alanine C3, γ-aminobutyric acid C2, C3 and C4 were obtained. A one-compartment model was used to fit 13C turnover curves and resulted in values of metabolic fluxes including the tricarboxylic acid (TCA) cycle flux VTCA (1.05 ± 0.04 μmol/g per minute), the exchange flux between 2-oxoglutarate and glutamate Vx (0.48 ± 0.02 μmol/g per minute), the glutamate-glutamine exchange rate Vgln (0.20 ± 0.02 μmol/g per minute), the pyruvate dilution factor Kdil (0.82 ± 0.01), and the ratio for the lactate conversion rate and the alanine conversion rate VLac/ VAla (10 ± 2). This study opens the prospect of studying transgenic mouse models of brain pathologies.

scholarly journals Regulation of murine myocardial energy metabolism during adrenergic stress studied by in vivo 31P NMR spectroscopy

2003 ◽  
Vol 285 (5) ◽  
pp. H1976-H1979 ◽  
Author(s):  
A. V. Naumova ◽  
R. G. Weiss ◽  
V. P. Chacko
Keyword(s):  
Heart Rate ◽  
Cardiac Metabolism ◽  
High Energy ◽  
Dobutamine Stress ◽  
Resonance Spectroscopy ◽  
31P Nmr Spectroscopy ◽  
Adult Mice ◽  
The Mean ◽  
Large Animals

Image-guided, spatially localized 31P magnetic resonance spectroscopy (MRS) was used to study in vivo murine cardiac metabolism under resting and dobutamine-induced stress conditions. Intravenous dobutamine infusion (24 μg · min–1 · kg body wt–1) increased the mean heart rate by ∼39% from 482 ± 46 per min at baseline to 669 ± 77 per min in adult mice. The myocardial phosphocreatine (PCr)-to-ATP (PCr/ATP) ratio remained unchanged at 2.1 ± 0.5 during dobutamine stress, compared with baseline conditions. Therefore, we conclude that a significant increase in heart rate does not result in a decline in the in vivo murine cardiac PCr/ATP ratio. These observations in very small mammals, viz., mice, at extremely high heart rates are consistent with studies in large animals demonstrating that global levels of high-energy phosphate metabolites do not regulate in vivo myocardial metabolism during physiologically relevant increases in cardiac work.

scholarly journals Excitatory/inhibitory neuronal metabolic balance in mouse hippocampus upon infusion of [U-13C6]glucose

2020 ◽  
pp. 0271678X2091053
Author(s):  
Antoine Cherix ◽  
Guillaume Donati ◽  
Blanca Lizarbe ◽  
Bernard Lanz ◽  
Carole Poitry-Yamate ◽  
...  
Keyword(s):  
Critical Role ◽  
Tca Cycle ◽  
Brain Regions ◽  
Inhibitory Neurons ◽  
Resonance Spectroscopy ◽  
Spectral Fitting ◽  
Mouse Hippocampus ◽  
And Behavior ◽  
Gabaergic Activity

Hippocampus plays a critical role in linking brain energetics and behavior typically associated to stress exposure. In this study, we aimed to simultaneously assess excitatory and inhibitory neuronal metabolism in mouse hippocampus in vivo by applying 18FDG-PET and indirect 13C magnetic resonance spectroscopy (1H-[13C]-MRS) at 14.1 T upon infusion of uniformly 13C-labeled glucose ([U-13C6]Glc). Improving the spectral fitting by taking into account variable decoupling efficiencies of [U-13C6]Glc and refining the compartmentalized model by including two γ-aminobutyric acid (GABA) pools permit us to evaluate the relative contributions of glutamatergic and GABAergic metabolism to total hippocampal neuroenergetics. We report that GABAergic activity accounts for ∼13% of total neurotransmission (VNT) and ∼27% of total neuronal TCA cycle (VTCA) in mouse hippocampus suggesting a higher VTCA/VNT ratio for inhibitory neurons compared to excitatory neurons. Finally, our results provide new strategies and tools for bringing forward the developments and applications of 13C-MRS in specific brain regions of small animals.

scholarly journals Compartmentalised energy metabolism supporting glutamatergic neurotransmission in response to increased activity in the rat cerebral cortex: A 13C MRS study in vivo at 14.1 T

2016 ◽  
Vol 36 (5) ◽  
pp. 928-940 ◽  
Author(s):  
Sarah Sonnay ◽  
João MN Duarte ◽  
Nathalie Just ◽  
Rolf Gruetter
Keyword(s):  
Energy Metabolism ◽  
Tca Cycle ◽  
Resonance Spectroscopy ◽  
Activity Levels ◽  
Rat Cortex ◽  
Metabolic Compartmentation ◽  
Specific Regulation ◽  
A Minor ◽  
Stimulation Of

Many tissues exhibit metabolic compartmentation. In the brain, while there is no doubt on the importance of functional compartmentation between neurons and glial cells, there is still debate on the specific regulation of pathways of energy metabolism at different activity levels. Using 13C magnetic resonance spectroscopy (MRS) in vivo, we determined fluxes of energy metabolism in the rat cortex under α-chloralose anaesthesia at rest and during electrical stimulation of the paws. Compared to resting metabolism, the stimulated rat cortex exhibited increased glutamate–glutamine cycle (+67 nmol/g/min, +95%, P < 0.001) and tricarboxylic (TCA) cycle rate in both neurons (+62 nmol/g/min, +12%, P < 0.001) and astrocytes (+68 nmol/g/min, +22%, P = 0.072). A minor, non-significant modification of the flux through pyruvate carboxylase was observed during stimulation (+5 nmol/g/min, +8%). Altogether, this increase in metabolism amounted to a 15% (67 nmol/g/min, P < 0.001) increase in CMRglc(ox), i.e. the oxidative fraction of the cerebral metabolic rate of glucose. In conclusion, stimulation of the glutamate–glutamine cycle under α-chloralose anaesthesia is associated to similar enhancement of neuronal and glial oxidative metabolism.

scholarly journals Cerebral Metabolism of Lactate in Vivo: Evidence for Neuronal Pyruvate Carboxylation

2000 ◽  
Vol 20 (2) ◽  
pp. 327-336 ◽  
Author(s):  
Bjørnar Hassel ◽  
Anders Bråthe
Keyword(s):  
Malic Enzyme ◽  
Specific Activity ◽  
Cerebral Metabolism ◽  
Resonance Spectroscopy ◽  
Pyruvate Carboxylation ◽  
Nitropropionic Acid ◽  
The Brain ◽  
Mitochondrial Malic Enzyme ◽  
Intrastriatal Injection

The cerebral metabolism of lactate was investigated. Awake mice received [3-13C]lactate or [1-13C]glucose intravenously, and brain and blood extracts were analyzed by 13C nuclear magnetic resonance spectroscopy. The cerebral up-take and metabolism of [3-13C]lactate was 50% that of [1-13C]glucose. [3-13C]Lactate was almost exclusively metabolized by neurons and hardly at all by glia, as revealed by the 13C labeling of glutamate, γ-aminobutyric acid and glutamine. Injection of [3-13C]lactate led to extensive formation of [2-13C]lactate, which was not seen with [1-13C]glucose, nor has it been seen in previous studies with [2-13C]acetate. This formation probably reflected reversible carboxylation of [3-13C]pyruvate to malate and equilibration with fumarate, because inhibition of succinate dehydrogenase with nitropropionic acid did not block it. Of the [3-13C]lactate that reached the brain, 20% underwent this reaction, which probably involved neuronal mitochondrial malic enzyme. The activities of mitochondrial malic enzyme, fumarase, and lactate dehydrogenase were high enough to account for the formation of [2-13C]lactate in neurons. Neuronal pyruvate carboxylation was confirmed by the higher specific activity of glutamate than of glutamine after intrastriatal injection of [1-14C]pyruvate into anesthetized mice. This procedure also demonstrated equilibration of malate, formed through pyruvate carboxylation, with fumarate. The demonstration of neuronal pyruvate carboxylation demands reconsideration of the metabolic interrelationship between neurons and glia.

scholarly journals The effects of therapeutic hypothermia on cerebral metabolism in neonates with hypoxic-ischemic encephalopathy: An in vivo 1H-MR spectroscopy study

2015 ◽  
Vol 36 (6) ◽  
pp. 1075-1086 ◽  
Author(s):  
Jessica L Wisnowski ◽  
Tai-Wei Wu ◽  
Aaron J Reitman ◽  
Claire McLean ◽  
Philippe Friedlich ◽  
...  
Keyword(s):  
Therapeutic Hypothermia ◽  
Energy Demand ◽  
Cerebral Metabolism ◽  
Brain Regions ◽  
Hypoxic Ischemic Encephalopathy ◽  
Cerebral White Matter ◽  
Similar Degree ◽  
Resonance Spectroscopy ◽  
Ischemic Encephalopathy

Therapeutic hypothermia has emerged as the first empirically supported therapy for neuroprotection in neonates with hypoxic-ischemic encephalopathy (HIE). We used magnetic resonance spectroscopy (1H-MRS) to characterize the effects of hypothermia on energy metabolites, neurotransmitters, and antioxidants. Thirty-one neonates with HIE were studied during hypothermia and after rewarming. Metabolite concentrations (mmol/kg) were determined from the thalamus, basal ganglia, cortical grey matter, and cerebral white matter. In the thalamus, phosphocreatine concentrations were increased by 20% during hypothermia when compared to after rewarming (3.49 ± 0.88 vs. 2.90 ± 0.65, p < 0.001) while free creatine concentrations were reduced to a similar degree (3.00 ± 0.50 vs. 3.74 ± 0.85, p < 0.001). Glutamate (5.33 ± 0.82 vs. 6.32 ± 1.12, p < 0.001), aspartate (3.39 ± 0.66 vs. 3.87 ± 1.19, p < 0.05), and GABA (0.92 ± 0.36 vs. 1.19 ± 0.41, p < 0.05) were also reduced, while taurine (1.39 ± 0.52 vs. 0.79 ± 0.61, p < 0.001) and glutathione (2.23 ± 0.41 vs. 2.09 ± 0.33, p < 0.05) were increased. Similar patterns were observed in other brain regions. These findings support that hypothermia improves energy homeostasis by decreasing the availability of excitatory neurotransmitters, and thereby, cellular energy demand.

scholarly journals Magnetic resonance spectroscopy of paragangliomas: new insights into in vivo metabolomics

2015 ◽  
Vol 22 (4) ◽  
pp. M1-M8 ◽  
Author(s):  
Arthur Varoquaux ◽  
Yann le Fur ◽  
Alessio Imperiale ◽  
Antony Reyre ◽  
Marion Montava ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Ex Vivo ◽  
Tca Cycle ◽  
Resonance Spectroscopy ◽  
Variants Of Unknown Significance ◽  
Neck Tumors ◽  
Single Voxel ◽  
Unknown Significance ◽  
Genetically Determined

Paragangliomas (PGLs) can be associated with mutations in genes of the tricarboxylic acid (TCA) cycle. Succinate dehydrogenase (SDHx) mutations are the prime examples of genetically determined TCA cycle defects with accumulation of succinate. Succinate, which acts as an oncometabolite, can be detected by ex vivo metabolomics approaches. The aim of this study was to evaluate the potential role of proton magnetic resonance (MR) spectroscopy (1H-MRS) for identifying SDHx-related PGLs in vivo and noninvasively. Eight patients were prospectively evaluated with single voxel 1H-MRS. MR spectra from eight tumors (four SDHx-related PGLs, two sporadic PGLs, one cervical schwannoma, and one cervical neurofibroma) were acquired and interpreted qualitatively. Compared to other tumors, a succinate resonance peak was detected only in SDHx-related tumor patients. Spectra quality was considered good in three cases, medium in two cases, poor in two cases, and uninterpretable in the latter case. Smaller lesions had lower spectra quality compared to larger lesions. Jugular PGLs also exhibited a poorer spectra quality compared to other locations. 1H-MRS has always been challenging in terms of its technical requisites. This is even more true for the evaluation of head and neck tumors. However, 1H-MRS might be added to the classical MR sequences for metabolomic characterization of PGLs. In vivo detection of succinate might guide genetic testing, characterize SDHx variants of unknown significance (in the absence of available tumor sample), and even optimize a selection of appropriate therapies.

scholarly journals Region-Specific Cerebral Metabolic Alterations in Streptozotocin-Induced Type 1 Diabetic Rats: An in vivo Proton Magnetic Resonance Spectroscopy Study

2015 ◽  
Vol 35 (11) ◽  
pp. 1738-1745 ◽  
Author(s):  
Hui Zhang ◽  
Mingming Huang ◽  
Lifeng Gao ◽  
Hao Lei
Keyword(s):  
Visual Cortex ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Brain Regions ◽  
Resonance Spectroscopy ◽  
Metabolic Disturbances ◽  
Metabolic Alterations ◽  
Neuronal Metabolism

Clinical and experimental in vivo1H-magnetic resonance spectroscopy (1H-MRS) studies have demonstrated that type 1 diabetes mellitus (T1DM) is associated with cerebral metabolic abnormalities. However, less is known whether T1DM induces different metabolic disturbances in different brain regions. In this study, in vivo1H-MRS was used to measure metabolic alterations in the visual cortex, striatum, and hippocampus of streptozotocin (STZ)-induced uncontrolled T1DM rats at 4 days and 4 weeks after induction. It was observed that altered neuronal metabolism occurred in STZ-treated rats as early as 4 days after induction. At 4 weeks, T1DM-related metabolic disturbances were clearly region specific. The diabetic visual cortex had more or less normal-appearing metabolic profile; while the striatum and hippocampus showed similar abnormalities in neuronal metabolism involving N-acetyl aspartate and glutamate; but only the hippocampus exhibited significant changes in glial markers such as taurine and myo-inositol. It is concluded that cerebral metabolic perturbations in STZ-induced T1DM rats are region specific at 4 weeks after induction, perhaps as a manifestation of varied vulnerability among the brain regions to sustained hyperglycemia.

scholarly journals The Contribution of Ketone Bodies to Basal and Activity-Dependent Neuronal Oxidation in Vivo

2014 ◽  
Vol 34 (7) ◽  
pp. 1233-1242 ◽  
Author(s):  
Golam MI Chowdhury ◽  
Lihong Jiang ◽  
Douglas L Rothman ◽  
Kevin L Behar
Keyword(s):  
Ketone Bodies ◽  
Ex Vivo ◽  
Brain Activity ◽  
Tca Cycle ◽  
Blood Levels ◽  
Neuronal Function ◽  
Energy Needs ◽  
Activity Dependent ◽  
Sufficient Concentration

The capacity of ketone bodies to replace glucose in support of neuronal function is unresolved. Here, we determined the contributions of glucose and ketone bodies to neocortical oxidative metabolism over a large range of brain activity in rats fasted 36 hours and infused intravenously with [2,4- 13 C2]-D-β-hydroxybutyrate (BHB). Three animal groups and conditions were studied: awake ex vivo, pentobarbital-induced isoelectricity ex vivo, and halothane-anesthetized in vivo, the latter data reanalyzed from a recent study. Rates of neuronal acetyl-CoA oxidation from ketone bodies ( VaccoA-kbN) and pyruvate ( VpdhN), and the glutamate-glutamine cycle ( Vcyc) were determined by metabolic modeling of 13C label trapped in major brain amino acid pools. VacCoA-kbN increased gradually with increasing activity, as compared with the steeper change in tricarboxylic acid (TCA) cycle rate ( VtcaN), supporting a decreasing percentage of neuronal ketone oxidation: ˜100% (isoelectricity), 56% (halothane anesthesia), 36% (awake) with the BHB plasma levels achieved in our experiments (6 to 13 mM). In awake animals ketone oxidation reached saturation for blood levels > 17 mM, accounting for 62% of neuronal substrate oxidation, the remainder (38%) provided by glucose. We conclude that ketone bodies present at sufficient concentration to saturate metabolism provides full support of basal (housekeeping) energy needs and up to approximately half of the activity-dependent oxidative needs of neurons.

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