2008
Glial pathology in an animal model of depression: reversal of stress-induced cellular, metabolic and behavioral deficits by the glutamate-modulating drug riluzole
Banasr M, Chowdhury GM, Terwilliger R, Newton SS, Duman RS, Behar KL, Sanacora G. Glial pathology in an animal model of depression: reversal of stress-induced cellular, metabolic and behavioral deficits by the glutamate-modulating drug riluzole. Molecular Psychiatry 2008, 15: 501-511. PMID: 18825147, PMCID: PMC3347761, DOI: 10.1038/mp.2008.106.Peer-Reviewed Original ResearchMeSH KeywordsAcetatesAnimalsAvoidance LearningBehavioral SymptomsDepressionDisease Models, AnimalFood PreferencesGene Expression RegulationGlial Fibrillary Acidic ProteinGlutamic AcidIsotopesMagnetic Resonance SpectroscopyMaleNeurogliaNeuroprotective AgentsPrefrontal CortexRadionuclide ImagingRatsRats, Sprague-DawleyRiluzoleRNA, MessengerStatistics, NonparametricStress, PsychologicalSucroseSweetening AgentsConceptsChronic unpredictable stressPrefrontal cortexGlial dysfunctionGlial functionBehavioral deficitsDrug riluzoleOpen-label clinical trialMRNA expressionAmino acid neurotransmissionAntidepressant drug developmentDepressive-like behaviorPathophysiology of depressionEffects of riluzoleGlial cell metabolismMajor depressive disorderRat prefrontal cortexGFAP mRNA expressionProtein mRNA expressionNeurotransmitter system abnormalitiesGlia pathologyGlial pathologyRiluzole treatmentAntidepressant actionChronic treatmentGlutamate release
2007
Glutamatergic and GABAergic Neurotransmitter Cycling and Energy Metabolism in Rat Cerebral Cortex during Postnatal Development
Chowdhury G, Patel AB, Mason GF, Rothman DL, Behar KL. Glutamatergic and GABAergic Neurotransmitter Cycling and Energy Metabolism in Rat Cerebral Cortex during Postnatal Development. Cerebrovascular And Brain Metabolism Reviews 2007, 27: 1895-1907. PMID: 17440492, DOI: 10.1038/sj.jcbfm.9600490.Peer-Reviewed Original ResearchMeSH KeywordsAcetatesAlgorithmsAmino AcidsAnimalsBlood GlucoseBrain ChemistryCerebral CortexCitric Acid CycleData Interpretation, StatisticalEnergy MetabolismGamma-Aminobutyric AcidGlucoseGlutamic AcidKineticsMagnetic Resonance SpectroscopyMaleNeurogliaNeuronsNeurotransmitter AgentsRatsRats, Sprague-DawleyConceptsNeurotransmitter cyclingThree-compartment metabolic modelEnergy metabolismRat cerebral cortexUrethane-anesthetized ratsPostnatal day 10Gamma-aminobutyric acidGABA neuronsTCA cycle fluxCerebral cortexAdult cortexPostnatal developmentDay 10Oxidative energy metabolismCycle fluxIndividual neuronsAcid levelsContribution of glutamatergicGrowth spurtNeuronsTricarboxylic acid cycle fluxAmino acid levelsTotal cyclingTime courseCortexAltered cerebral glucose and acetate metabolism in succinic semialdehyde dehydrogenase‐deficient mice: evidence for glial dysfunction and reduced glutamate/glutamine cycling
Chowdhury GM, Gupta M, Gibson KM, Patel AB, Behar KL. Altered cerebral glucose and acetate metabolism in succinic semialdehyde dehydrogenase‐deficient mice: evidence for glial dysfunction and reduced glutamate/glutamine cycling. Journal Of Neurochemistry 2007, 103: 2077-2091. PMID: 17854388, DOI: 10.1111/j.1471-4159.2007.04887.x.Peer-Reviewed Original ResearchMeSH KeywordsAcetatesAmino AcidsAnimalsAnimals, NewbornBlood GlucoseCarbon IsotopesCerebral CortexGamma-Aminobutyric AcidGlutamate-Ammonia LigaseGlutamic AcidGlutamineImage Processing, Computer-AssistedMagnetic Resonance SpectroscopyMiceMice, KnockoutNeurogliaSodium OxybateSuccinate-Semialdehyde DehydrogenaseTime FactorsConceptsSSADH deficiencyLevels of GABAGlutamate/glutamine cyclingSuccinic semialdehyde dehydrogenase‐deficient miceGlutamine-C4Cerebral metabolismCerebral glucoseCortical extractsGlial dysfunctionIntraperitoneal infusionSuccinic semialdehyde dehydrogenaseGABA-C2Excessive elevationNeurotransmitter glutamateGABA synthesisGABAMiceGHBGlutamateGlutamine metabolismAspartate C3GliaCortexGlutamine cyclingGlial substrate
2006
Neuronal–Glial Glucose Oxidation and Glutamatergic–GABAergic Function
Hyder F, Patel AB, Gjedde A, Rothman DL, Behar KL, Shulman RG. Neuronal–Glial Glucose Oxidation and Glutamatergic–GABAergic Function. Cerebrovascular And Brain Metabolism Reviews 2006, 26: 865-877. PMID: 16407855, DOI: 10.1038/sj.jcbfm.9600263.Peer-Reviewed Original ResearchConceptsGamma-amino butyric acid (GABA) neuronsNeuronal glucose oxidationGlutamate-glutamine cyclingRelease of lactateGlucose oxidationNeuronal oxidationGlial uptakeGABAergic neuronsGlutamate uptakeGliaNeuronsGlycolytic ATPLactateGlucoseTotal glucoseVivo rateIsoelectricityCulture studiesATPNeurotransmittersUptake
2001
Glutamine is the major precursor for GABA synthesis in rat neocortex in vivo following acute GABA-transaminase inhibition
Patel A, Rothman D, Cline G, Behar K. Glutamine is the major precursor for GABA synthesis in rat neocortex in vivo following acute GABA-transaminase inhibition. Brain Research 2001, 919: 207-220. PMID: 11701133, DOI: 10.1016/s0006-8993(01)03015-3.Peer-Reviewed Original ResearchIn Vivo Nuclear Magnetic Resonance Studies of Glutamate-γ-Aminobutyric Acid-Glutamine Cycling in Rodent and Human Cortex: the Central Role of Glutamine
Behar K, Rothman D. In Vivo Nuclear Magnetic Resonance Studies of Glutamate-γ-Aminobutyric Acid-Glutamine Cycling in Rodent and Human Cortex: the Central Role of Glutamine. Journal Of Nutrition 2001, 131: 2498s-2504s. PMID: 11533301, DOI: 10.1093/jn/131.9.2498s.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsGamma-aminobutyric acidGlutamate-GABACortical glucose utilizationCortical electrical activityNet glutamine synthesisCerebral cortexInhibitory neurotransmitterMajor excitatoryBrain glutamateGlutamine synthesisNeurotransmitter glutamateRodent cortexGlucose utilizationHuman cortexGlutamine cycleElectrical activityCortexCentral roleGlutamine cyclingCommon mechanismGlucose oxidationGlutamateVivo nuclear magnetic resonance studiesRodentsGlutamineDecrease in GABA synthesis rate in rat cortex following GABA-transaminase inhibition correlates with the decrease in GAD67 protein
Mason G, Martin D, Martin S, Manor D, Sibson N, Patel A, Rothman D, Behar K. Decrease in GABA synthesis rate in rat cortex following GABA-transaminase inhibition correlates with the decrease in GAD67 protein. Brain Research 2001, 914: 81-91. PMID: 11578600, DOI: 10.1016/s0006-8993(01)02778-0.Peer-Reviewed Original ResearchConceptsTotal GAD activityGAD activityNon-treated control groupGABA-transaminase inhibitionNitrous oxide anesthesiaCortex of controlGlutamate-glutamine cyclingGlutamic acid decarboxylaseGABA synthesis rateGamma-aminobutyric acid (GABA) synthesisVigabatrin treatmentOxide anesthesiaRat cortexGAD67 proteinControl groupBasal conditionsAcid decarboxylaseEx vivoNeuronal compartmentsVigabatrinQuantitative immunoblottingIsoform compositionRatsCortexInhibitionInhibition of Voltage-Dependent Sodium Channels Suppresses the Functional Magnetic Resonance Imaging Response to Forepaw Somatosensory Activation in the Rodent
Kida I, Hyder F, Behar K. Inhibition of Voltage-Dependent Sodium Channels Suppresses the Functional Magnetic Resonance Imaging Response to Forepaw Somatosensory Activation in the Rodent. Cerebrovascular And Brain Metabolism Reviews 2001, 21: 585-591. PMID: 11333369, DOI: 10.1097/00004647-200105000-00013.Peer-Reviewed Original ResearchConceptsMagnetic resonance imaging responseSomatosensory activationFunctional magnetic resonance imaging (fMRI) responsesForepaw stimulationLamotrigine treatmentImaging responseGlutamate release inhibitorBOLD fMRI responsesFunctional imaging signalsBOLD fMRI signal changesFMRI signal changesTime-dependent mannerBaseline CBFAbsence of stimulationSomatosensory cortexRelease inhibitorChannel blockersRat cortexNeurotransmitter cycleBlood flow experimentsFMRI responsesBOLD fMRIStimulationLamotrigineTreatmentIn vivo13C NMR measurement of neurotransmitter glutamate cycling, anaplerosis and TCA cycle flux in rat brain during [2‐13C]glucose infusion
Sibson N, Mason G, Shen J, Cline G, Herskovits A, Wall J, Behar K, Rothman D, Shulman R. In vivo13C NMR measurement of neurotransmitter glutamate cycling, anaplerosis and TCA cycle flux in rat brain during [2‐13C]glucose infusion. Journal Of Neurochemistry 2001, 76: 975-989. PMID: 11181817, DOI: 10.1046/j.1471-4159.2001.00074.x.Peer-Reviewed Original ResearchConceptsGlutamate/glutamine cyclingCerebral cortexAstrocytic tricarboxylic acid cycleGlutamine cyclingRat cerebral cortexGlutamine synthesisDe novo glutamine synthesisAnesthetized ratsRat brainNeurotransmitter glutamateHyperammonemic conditionsGlutamate cyclingInfusionGlutamate precursorCortexBrainTCA cycle fluxAnaplerosisMajor metabolic fluxTricarboxylic acid cycleCycle flux
1999
In vivo nuclear magnetic resonance spectroscopy studies of the relationship between the glutamate--glutamine neurotransmitter cycle and functional neuroenergetics
Rothman D, Sibson N, Hyder F, Shen J, Behar K, Shulman R. In vivo nuclear magnetic resonance spectroscopy studies of the relationship between the glutamate--glutamine neurotransmitter cycle and functional neuroenergetics. Philosophical Transactions Of The Royal Society B Biological Sciences 1999, 354: 1165-1177. PMID: 10466144, PMCID: PMC1692640, DOI: 10.1098/rstb.1999.0472.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsGlutamate-glutamine cycleNerve terminalsNeurotransmitter cycleGlucose metabolismBlood oxygenation level-dependent magnetic resonance imagingLevel-dependent magnetic resonance imagingBrain glucose oxidationCortical glucose metabolismMagnetic resonance spectroscopy studyCortex of ratsMagnetic resonance imagingFunctional imaging studiesSpecific neuronal activityOxidative glucose metabolismGlial cellsNeuronal activityResonance imagingImaging studiesHuman cortexBrain functionBrain activityRatsCortexGlucose oxidationGlutamateDetermination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR
Shen J, Petersen K, Behar K, Brown P, Nixon T, Mason G, Petroff O, Shulman G, Shulman R, Rothman D. Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 8235-8240. PMID: 10393978, PMCID: PMC22218, DOI: 10.1073/pnas.96.14.8235.Peer-Reviewed Original ResearchConceptsGlutamate/glutamine cycleGlutamine cycleCerebral cortexMin/Rat cerebral cortexVivo 13C NMR spectraGlucose oxidation ratesHuman brainGlucose oxidationGlutamatergic activityRat modelTricarboxylic acid cycle rateParietal lobeHuman cortexCortexTime courseBrainGlutamine synthesisMajor metabolic fluxCycle rateTricarboxylic acid cycleHigh levelsInfusionRatsAcid cycle
1998
Functional Energy Metabolism:In vivo 13C-NMR Spectroscopy Evidence for Coupling of Cerebral Glucose Consumption and Gl utamatergic Neuronal Activity
Sibson N, Shen J, Mason G, Rothman D, Behar K, Shulman R. Functional Energy Metabolism:In vivo 13C-NMR Spectroscopy Evidence for Coupling of Cerebral Glucose Consumption and Gl utamatergic Neuronal Activity. Developmental Neuroscience 1998, 20: 321-330. PMID: 9778568, DOI: 10.1159/000017327.Peer-Reviewed Original ResearchConceptsRat brain cortexGlucose metabolismBrain cortexNeurotransmitter cyclingTotal glucose oxidationGlutamatergic synaptic activityCerebral glucose consumptionCerebral glucose metabolismFunctional activityFunctional imaging methodsGlucose oxidationOxidative glucose metabolismGlutamate neurotransmitter cyclingSynaptic activityNeuronal activityMild anesthesiaGlutamine synthesisMammalian brainNeurotransmitter releaseGlutamate cyclingEEG activityAmmonia metabolismNeurophysiological basisDetoxification componentsVivo results15N-NMR Spectroscopy Studies of Ammonia Transport and Glutamine Synthesis in the Hyperammonemic Rat Brain
Shen J, Sibson N, Cline G, Behar K, Rothman D, Shulman R. 15N-NMR Spectroscopy Studies of Ammonia Transport and Glutamine Synthesis in the Hyperammonemic Rat Brain. Developmental Neuroscience 1998, 20: 434-443. PMID: 9778582, DOI: 10.1159/000017341.Peer-Reviewed Original Research
1997
In vivo 13C NMR measurements of cerebral glutamine synthesis as evidence for glutamate–glutamine cycling
Sibson N, Dhankhar A, Mason G, Behar K, Rothman D, Shulman R. In vivo 13C NMR measurements of cerebral glutamine synthesis as evidence for glutamate–glutamine cycling. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 2699-2704. PMID: 9122259, PMCID: PMC20152, DOI: 10.1073/pnas.94.6.2699.Peer-Reviewed Original Research
1995
Initial Observations on Effect of Vigabatrin on In Vivo 1H Spectroscopic Measurements of γ‐Aminobutyric Acid, Glutamate, and Glutamine in Human Brain
Petroff O, Rothman D, Behar K, Mattson R. Initial Observations on Effect of Vigabatrin on In Vivo 1H Spectroscopic Measurements of γ‐Aminobutyric Acid, Glutamate, and Glutamine in Human Brain. Epilepsia 1995, 36: 457-464. PMID: 7614922, DOI: 10.1111/j.1528-1157.1995.tb00486.x.Peer-Reviewed Original ResearchConceptsGamma-aminobutyric acidGABA levelsMumol/Antiepileptic drugsOccipital GABA levelsEffective antiepileptic drugEffects of vigabatrinStandard medicationStandard doseΓ-aminobutyric acidHealthy subjectsEpileptic patientsVigabatrinPatientsGABA transaminaseHuman cerebrumNoninvasive measurementHuman brainBrainGlutamateInitial observationsMedicationsCerebrumLevelsDoseSimultaneous Determination of the Rates of the TCA Cycle, Glucose Utilization, α-Ketoglutarate/Glutamate Exchange, and Glutamine Synthesis in Human Brain by NMR
Mason G, Gruetter R, Rothman D, Behar K, Shulman R, Novotny E. Simultaneous Determination of the Rates of the TCA Cycle, Glucose Utilization, α-Ketoglutarate/Glutamate Exchange, and Glutamine Synthesis in Human Brain by NMR. Cerebrovascular And Brain Metabolism Reviews 1995, 15: 12-25. PMID: 7798329, DOI: 10.1038/jcbfm.1995.2.Peer-Reviewed Original Research
1994
Analysis of macromolecule resonances in 1H NMR spectra of human brain
Behar K, Rothman D, Spencer D, Petroff O. Analysis of macromolecule resonances in 1H NMR spectra of human brain. Magnetic Resonance In Medicine 1994, 32: 294-302. PMID: 7984061, DOI: 10.1002/mrm.1910320304.Peer-Reviewed Original ResearchMeasurement of GABA following GABA‐transaminase inhibition by gabaculine: A 1H and 31P NMR spectroscopic study of rat brain in vivo
Behar K, Boehm D. Measurement of GABA following GABA‐transaminase inhibition by gabaculine: A 1H and 31P NMR spectroscopic study of rat brain in vivo. Magnetic Resonance In Medicine 1994, 31: 660-667. PMID: 7914662, DOI: 10.1002/mrm.1910310612.Peer-Reviewed Original ResearchMeSH Keywords4-Aminobutyrate TransaminaseAnimalsAspartic AcidBrainBrain ChemistryCreatineCyclohexanecarboxylic AcidsGamma-Aminobutyric AcidGlutamatesGlutamic AcidHydrogenHydrogen-Ion ConcentrationMagnetic Resonance SpectroscopyMaleNucleotidesPhosphatesPhosphocreatinePhosphorusRatsRats, Sprague-Dawley
1992
NMR Determination of the TCA Cycle Rate and α-Ketoglutarate/Glutamate Exchange Rate in Rat Brain
Mason G, Rothman D, Behar K, Shulman R. NMR Determination of the TCA Cycle Rate and α-Ketoglutarate/Glutamate Exchange Rate in Rat Brain. Cerebrovascular And Brain Metabolism Reviews 1992, 12: 434-447. PMID: 1349022, DOI: 10.1038/jcbfm.1992.61.Peer-Reviewed Original Research
1991
Assignment of resonances in the 1H spectrum of rat brain by two‐dimensional shift correlated and j‐resolved NMR spectroscopy
Behar K, Ogino T. Assignment of resonances in the 1H spectrum of rat brain by two‐dimensional shift correlated and j‐resolved NMR spectroscopy. Magnetic Resonance In Medicine 1991, 17: 285-303. PMID: 1676483, DOI: 10.1002/mrm.1910170202.Peer-Reviewed Original Research