scholarly journals Altered 13C Glucose Metabolism in the Cortico—Striato—Thalamo—Cortical Loop in the MK-801 Rat Model of Schizophrenia

2010 ◽  
Vol 31 (3) ◽  
pp. 976-985 ◽  
Author(s):  
Elvar M Eyjolfsson ◽  
Linn Hege Nilsen ◽  
Daniel Kondziella ◽  
Eiliv Brenner ◽  
Asta Håberg ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
High Performance ◽  
Temporal Cortex ◽  
Gas Chromatography Mass Spectrometry ◽  
Resonance Spectroscopy ◽  
Dopamine Turnover ◽  
Mk 801 ◽  
Pronounced Reduction ◽  
Monoaminergic Neurotransmitter ◽  
Synthesis And Degradation

Using a modified MK-801 (dizocilpine) N-methyl-d-aspartic acid (NMDA) receptor hypofunction model for schizophrenia, we analyzed glycolysis, as well as glutamatergic, GABAergic, and monoaminergic neurotransmitter synthesis and degradation. Rats received an injection of MK-801 daily for 6 days and on day 6, they also received an injection of [1-13C]glucose. Extracts of frontal cortex (FCX), parietal and temporal cortex (PTCX), thalamus, striatum, nucleus accumbens (NAc), and hippocampus were analyzed using 13C nuclear magnetic resonance spectroscopy, high-performance liquid chromatography, and gas chromatography—mass spectrometry. A pronounced reduction in glycolysis was found only in PTCX, in which 13C labeling of glucose, lactate, and alanine was decreased. 13C enrichment in lactate, however, was reduced in all areas investigated. The largest reductions in glutamate labeling were detected in FCX and PTCX, whereas in hippocampus, striatum, and Nac, 13C labeling of glutamate was only slightly but significantly reduced. The thalamus was the only region with unaffected glutamate labeling. γ-Aminobutyric acid (GABA) labeling was reduced in all areas, but most significantly in FCX. Glutamine and aspartate labeling was unchanged. Mitochondrial metabolites were also affected. Fumarate labeling was reduced in FCX and thalamus, whereas malate labeling was reduced in FCX, PTCX, striatum, and NAc. Dopamine turnover was decreased in FCX and thalamus, whereas that of serotonin was unchanged in all regions. In conclusion, neurotransmitter metabolism in the cortico—striato—thalamo—cortical loop is severely impaired in the MK-801 (dizocilpine) NMDA receptor hypofunction animal model for schizophrenia.

scholarly journals In vivo glucose metabolism and glutamate levels in mGluR5 knockout mice: a multimodal neuroimaging study using [18F]FDG microPET and MRS

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yo-Han Joo ◽  
Yun-Kwan Kim ◽  
In-Gyu Choi ◽  
Hyeon-Jin Kim ◽  
Young-Don Son ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Glucose Metabolism ◽  
Cerebral Glucose Metabolism ◽  
Functional Coupling ◽  
Resonance Spectroscopy ◽  
Acute Administration ◽  
Multimodal Neuroimaging ◽  
Mk 801 ◽  
Genetic Ablation ◽  
Neuroimaging Study

Abstract Background Perturbed functional coupling between the metabotropic glutamate receptor-5 (mGluR5) and N-methyl-d-aspartate (NMDA) receptor-mediated excitatory glutamatergic neurotransmission may contribute to the pathophysiology of psychiatric disorders such as schizophrenia. We aimed to establish the functional interaction between mGluR5 and NMDA receptors in brain of mice with genetic ablation of the mGluR5. Methods We first measured the brain glutamate levels with magnetic resonance spectroscopy (MRS) in mGluR5 knockout (KO) and wild-type (WT) mice. Then, we assessed brain glucose metabolism with [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography before and after the acute administration of an NMDA antagonist, MK-801 (0.5 mg/kg), in the same mGluR5 KO and WT mice. Results Between-group comparisons showed no significant differences in [18F]FDG standardized uptake values (SUVs) in brain of mGluR5 KO and WT mice at baseline, but widespread reductions in mGluR5 KO mice compared to WT mice after MK-801 administration (p < 0.05). The baseline glutamate levels did not differ significantly between the two groups. However, there were significant negative correlations between baseline prefrontal glutamate levels and regional [18F]FDG SUVs in mGluR5 KO mice (p < 0.05), but no such correlations in WT mice. Fisher’s Z-transformation analysis revealed significant between-group differences in these correlations (p < 0.05). Conclusions This is the first multimodal neuroimaging study in mGluR5 KO mice and the first report on the association between cerebral glucose metabolism and glutamate levels in living rodents. The results indicate that mGluR5 KO mice respond to NMDA antagonism with reduced cerebral glucose metabolism, suggesting that mGluR5 transmission normally moderates the net effects of NMDA receptor antagonism on neuronal activity. The negative correlation between glutamate levels and glucose metabolism in mGluR5 KO mice at baseline may suggest an unmasking of an inhibitory component of the glutamatergic regulation of neuronal energy metabolism.

scholarly journals Glutamate Metabolism is Impaired in Transgenic Mice with Tau Hyperphosphorylation

2013 ◽  
Vol 33 (5) ◽  
pp. 684-691 ◽  
Author(s):  
Linn Hege Nilsen ◽  
Caroline Rae ◽  
Lars M Ittner ◽  
Jürgen Götz ◽  
Ursula Sonnewald
Keyword(s):  
Cerebral Cortex ◽  
Transgenic Mice ◽  
High Performance ◽  
Pathogenic Mutation ◽  
Relative Increase ◽  
Gas Chromatography Mass Spectrometry ◽  
Resonance Spectroscopy ◽  
Tau Hyperphosphorylation ◽  
Hypermetabolic State ◽  
Carboxylation Pathway

In neurodegenerative diseases including Alzheimer's disease and frontotemporal dementia, the protein tau is hyperphosphorylated and eventually aggregates to develop neurofibrillary tangles. Here, the consequences of tau hyperphosphorylation on both neuronal and astrocytic metabolism and amino-acid neurotransmitter homeostasis were assessed in transgenic mice expressing the pathogenic mutation P301L in the human tau gene (pR5 mice) compared with nontransgenic littermate controls. Mice were injected with the neuronal and astrocytic substrate [1-13C]glucose and the astrocytic substrate [1,2-13C]acetate. Hippocampus and cerebral cortex extracts were analyzed using 1H and 13C nuclear magnetic resonance spectroscopy, gas chromatography–mass spectrometry and high-performance liquid chromatography. The glutamate level was reduced in the hippocampus of pR5 mice, accompanied by reduced incorporation of 13C label derived from [1-13C]glucose in glutamate. In the cerebral cortex, glucose utilization as well as turnover of glutamate, glutamine, and GABA, were increased. This was accompanied by a relative increase in production of glutamate via the pyruvate carboxylation pathway in cortex. Overall, we revealed that astrocytes as well as glutamatergic and GABAergic neurons in the cortex of pR5 mice were in a hypermetabolic state, whereas in the hippocampus, where expression levels of mutant human tau are the highest, glutamate homeostasis was impaired.

Alkalemia reduces recovery from global cerebral ischemia by NMDA receptor-mediated mechanism

1997 ◽  
Vol 272 (6) ◽  
pp. H2557-H2562
Author(s):  
P. D. Hurn ◽  
R. C. Koehler ◽  
R. J. Traystman
Keyword(s):  
Energy Metabolism ◽  
Cerebral Ischemia ◽  
Nmda Receptor ◽  
Nmda Receptor Antagonist ◽  
Global Cerebral Ischemia ◽  
Resonance Spectroscopy ◽  
Mk 801 ◽  
Sagittal Sinus

In vitro data suggest that low tissue pH reduces, whereas extracellular alkalosis potentiates, cerebral anoxic injury via excitotoxic mechanisms. We tested the hypothesis that in vivo metabolic alkalemia potentiates defects in energy metabolism after global incomplete cerebral ischemia (12 min) and reperfusion (180 min) by an N-methyl-D-aspartate (NMDA) receptor-mediated mechanism. Brain ATP, phosphocreatine, and intracellular pH (pHi) were measured by 31P magnetic resonance spectroscopy in anesthetized dogs treated with 1) preischemic intravenous carbicarb buffer (NaHCO3+Na2CO3, Carb, n = 7); 2) carbicarb infusion plus NMDA receptor antagonist MK-801 (MK-801 + Carb, n = 7); 3) an osmotically equivalent volume of 5% NaCl (NaCl, n = 8); or 4) equivalent volume of 0.9% NaCl (Sal, n = 3). Sagittal sinus pH was raised to 7.82 +/- 0.04 before and 7.65 +/- 0.03 during ischemia in Carb vs. 7.72 +/- 0.01 and 7.60 +/- 0.01 in MK-801+Carb, 7.25 +/- 0.02 and 7.15 +/- 0.03 in NaCl, and 7.31 +/- 0.00 and 7.26 +/- 0.01 in Sal, respectively. Ischemic cerebral blood flow (CBF, radiolabeled microspheres), pHi, and ATP reduction were similar among groups. By 180 min of reperfusion, recovery of ATP was greater in MK-801+Carb (104 +/- 6% of baseline), NaCl (93 +/- 6%), and Sal (94 +/- 6%) than in Carb (47 +/- 6%). Intraischemic pHi was similar among groups, and pHi recovery did not vary among groups despite differences in sagittal sinus pH. In Carb, CBF was restored but with delayed hypoperfusion. We conclude that extracellular alkalosis is deleterious to postischemic CBF and energy metabolism, acting by NMDA receptor-mediated mechanisms.

Identification of new lignans in Norway spruce knotwood extracts

Holzforschung ◽  
2012 ◽  
Vol 66 (5) ◽  
pp. 553-567 ◽  
Author(s):  
Annika I. Smeds ◽  
Iveta Češková ◽  
Patrik C. Eklund ◽  
Stefan M. Willför
Keyword(s):  
Mass Spectrometry ◽  
Norway Spruce ◽  
High Performance ◽  
Mass Spectra ◽  
Ethanol Extract ◽  
Dry Weight ◽  
Flash Chromatography ◽  
Gas Chromatography Mass Spectrometry ◽  
Resonance Spectroscopy ◽  
Hydrophilic Extract

Abstract In a hydrophilic extract of Norway spruce knotwood, the dominating lignan, 7-hydroxymatairesinol, was partially removed by precipitation, and the resulting mixture was fractionated by flash chromatography and preparative high-performance liquid chromatography (HPLC). In the HPLC fractions, 7S- and 7R-todolactol A, 7′-hydroxylariciresinol, and two stereoisomers of 9′-hydroxylariciresinol were identified by gas chromatography-mass spectrometry (GC-MS) analyses, and their structures were confirmed by nuclear magnetic resonance spectroscopy. The 9′-hydroxylariciresinols were suggested to have the 7S,8R,8′R,9′Rand 7R,8R,8′R,9′Rconfigurations, and (-)-7′-hydroxylariciresinol 7S*,7′R*,8R*,8′S*, which indicates a configuration of this structure that has not been reported previously. 7S- and 7R-isoliovil were identified by comparison with previously published GC-MS data, and 7′-oxolariciresinol was tentatively identified on the basis of its mass spectrum. Of these lignans, only 7′-hydroxylariciresinol has been identified previously in Norway spruce. Several other lignans with similar mass spectra as the todolactols, isoliovils, and 7′-hydroxylariciresinol were detected, indicating that they are different stereoisomers of these lignans and/or of liovils. In addition to these lignans, the mass spectra of several other unidentified minor lignans indicated the presence of several tens of previously unidentified minor lignans in Norway spruce knotwood, accounting altogether for approximately 6% of the dry weight of the ethanol extract. 7S-Todolactol A, which was dominating among the new lignans, was found to be very unstable in aqueous solutions. Identification of more of these unidentified lignans may be possible only by access to pure reference compounds.

Isolation and Characterization of a Dibenzofuran-Degrading Yeast: Identification of Oxidation and Ring Cleavage Products

1998 ◽  
Vol 64 (6) ◽  
pp. 2215-2219 ◽  
Author(s):  
Elke Hammer ◽  
Dirk Krowas ◽  
Annett Schäfer ◽  
Michael Specht ◽  
Wittko Francke ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Performance ◽  
Analytical Data ◽  
Gas Chromatography Mass Spectrometry ◽  
Ring Cleavage ◽  
Resonance Spectroscopy ◽  
Yeast Identification ◽  
Isolation And Characterization ◽  
Incubation Experiments

ABSTRACT We characterized the ability of a yeast to cleave the aromatic structure of the dioxin-like compound dibenzofuran. The yeast strain was isolated from a dioxin-contaminated soil sample and identified asTrichosporon mucoides. During incubation of glucose-pregrown cells with dibenzofuran, six major metabolites were detected by high-performance liquid chromatography. The formation of four different monohydroxylated dibenzofurans was proven by comparison of analytical data (gas chromatography-mass spectrometry) with that for authentic standards. Further oxidation produced 2,3-dihydroxydibenzofuran and its ring cleavage product 2-(1-carboxy methylidene)-2,3-dihydrobenzo[b]furanylidene glycolic acid, which were characterized by mass spectrometry and 1H nuclear magnetic resonance spectroscopy. These two metabolites are derived from 2-hydroxydibenzofuran and 3-hydroxydibenzofuran, as shown by incubation experiments using these monohydroxylated dibenzofurans as substrates.

Superionic Lithium Intercalation through 2 nm x 2 nm Columns in the Crystallographic Shear Phase Nb18W8O69

2019 ◽  
Author(s):  
Kent Griffith ◽  
Clare Grey
Keyword(s):  
High Performance ◽  
Rate Capability ◽  
Block Size ◽  
Lithium Intercalation ◽  
Resonance Spectroscopy ◽  
Complex Metal Oxides ◽  
Battery Electrode ◽  
Crystallographic Shear ◽  
Battery Material ◽  
First Time

Nb18W8O69 (9Nb2O5×8WO3) is the tungsten-rich end-member of the Wadsley–Roth crystallographic shear (cs) structures within the Nb2O5–WO3 series. It has the largest block size of any known, stable Wadsley–Roth phase, comprising 5 ´ 5 units of corner-shared MO6 octahedra between the shear planes, giving rise to 2 nm ´ 2 nm blocks. Rapid lithium intercalation is observed in this new candidate battery material and 7Li pulsed field gradient nuclear magnetic resonance spectroscopy – measured in a battery electrode for the first time at room temperature – reveals superionic lithium conductivity. In addition to its promising rate capability, Nb18W8O69 adds a piece to the larger picture of our understanding of high-performance Wadsley–Roth complex metal oxides.

Application of a fractionation technique for better understanding of the removal of natural organic matter by alum coagulation

2002 ◽  
Vol 2 (5-6) ◽  
pp. 427-433 ◽  
Author(s):  
J. van Leeuwen ◽  
C. Chow ◽  
R. Fabris ◽  
N. Withers ◽  
D. Page ◽  
...  
Keyword(s):  
Organic Matter ◽  
Natural Organic Matter ◽  
High Performance ◽  
Relative Proportion ◽  
Water Source ◽  
Size Exclusion ◽  
Gas Chromatography Mass Spectrometry ◽  
Pyrolysis Gas ◽  
Alum Treatment ◽  
Hydrophobic Acids

To gain an improved understanding of the types of organic compounds that are recalcitrant to water treatment, natural organic matter (NOM) isolates from two drinking water sources (Mt. Zero and Moorabool reservoirs, Victoria, Australia) were separated into fractions of distinct chemical behaviour using resins. Four fractions were obtained from each water source and were organics absorbed to: (1) XAD-8 (very hydrophobic acids, VHA); (2) DAX-4 (slightly hydrophobic acids, SHA); (3) bound to an anion exchange resin (charged organics, CHAR); and (4) not absorbed or bound to resins (neutrals, NEUT). These fractions were then tested to determine the capacity of alum to remove them from water and to correlate this with the character of each isolate. The fractions were characterised by the application of high performance size exclusion chromatography (HPSEC), bacterial regrowth potential (BRP), trihalomethane formation potential (THMFP), pyrolysis gas-chromatography mass spectrometry (Py-GC-MS) and thermochemolysis. The highest removals of dissolved organic carbon (DOC) by alum treatment were in waters spiked with the CHAR fractions while the NEUT fractions were the most recalcitrant. The number average molecular weights (Mn) of DOC of the CHAR fractions before treatment were the highest, whilst those of the NEUT fractions were the lowest. After alum treatment, the Mn of the NEUT fractions were only slightly reduced. Results from Py-GC-MS and thermochemolysis indicate that the NEUT fractions had the highest relative proportion of saccharide derived organic material. Nonetheless, the BRP of waters spiked with the NEUT fractions differed markedly, indicating that organics recalcitrant to alum treatment can vary substantially in their chemical composition and capacity to support microbial growth.

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