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 courseCortex
2006
Evidence that GAD65 mediates increased GABA synthesis during intense neuronal activity in vivo
Patel AB, de Graaf RA, Martin DL, Battaglioli G, Behar KL. Evidence that GAD65 mediates increased GABA synthesis during intense neuronal activity in vivo. Journal Of Neurochemistry 2006, 97: 385-396. PMID: 16539672, DOI: 10.1111/j.1471-4159.2006.03741.x.Peer-Reviewed Original ResearchMeSH Keywords4-Aminobutyrate TransaminaseAnimalsAnticonvulsantsBicucullineBlotting, WesternDose-Response Relationship, DrugGABA AntagonistsGamma-Aminobutyric AcidGlutamate DecarboxylaseIsoenzymesMagnetic Resonance SpectroscopyMaleProtein IsoformsRatsRats, Sprague-DawleySeizuresTime FactorsVigabatrin
2001
Quantitative functional imaging of the brain: towards mapping neuronal activity by BOLD fMRI
Hyder F, Kida I, Behar K, Kennan R, Maciejewski P, Rothman D. Quantitative functional imaging of the brain: towards mapping neuronal activity by BOLD fMRI. NMR In Biomedicine 2001, 14: 413-431. PMID: 11746934, DOI: 10.1002/nbm.733.Peer-Reviewed Original ResearchConceptsMagnetic resonance imagingNeuronal activityBOLD functional MRIFunctional MRICerebral cortexPharmacological treatmentGlutamate release inhibitorNeuronal glucose oxidationRat cerebral cortexRelease of glutamateRat forepaw stimulation modelFMRI signalsFunctional magnetic resonance imagingQuantitative magnetic resonance imagingBlood oxygenation levelBOLD fMRI studiesEnergy metabolismBOLD fMRI signalMulti-modal magnetic resonance imagingGlutamatergic neuronsRelease inhibitorChannel blockersRat brainOxygen deliveryNeurochemical basisGlutamine 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 fluxDifferential increase in cerebral cortical glucose oxidative metabolism during rat postnatal development is greater in vivo than in vitro
Novotny E, Ariyan C, Mason G, O’Reilly J, Haddad G, Behar K. Differential increase in cerebral cortical glucose oxidative metabolism during rat postnatal development is greater in vivo than in vitro. Brain Research 2001, 888: 193-202. PMID: 11150475, DOI: 10.1016/s0006-8993(00)03051-1.Peer-Reviewed Original ResearchConceptsGlucose oxidative metabolismNeocortical slicesOxidative metabolismRat postnatal developmentCortical glutamateCerebral cortexCortex maturesPostnatal dayPostnatal developmentAge groupsCortexMitochondrial TCA cycleGreater increaseVivoGlucose oxidationTCA cycle fluxDifferential increaseAcid extractsMetabolismSlicesDeafferentiationCycle fluxRats
2000
Brain regional development of the activity of α-ketoglutarate dehydrogenase complex in the rat
Buerstatte C, Behar K, Novotny E, Lai J. Brain regional development of the activity of α-ketoglutarate dehydrogenase complex in the rat. Brain Research 2000, 125: 139-145. PMID: 11154769, DOI: 10.1016/s0165-3806(00)00134-6.Peer-Reviewed Original ResearchConceptsAdult levelsKGDHC activityCerebral cortexOlfactory bulbPostnatal day 2Age-dependent increaseGlucose oxidative metabolismAlpha-ketoglutarate dehydrogenase complex activityRat brainDay 2Pathophysiological implicationsPostnatal developmentDistinct region-specific patternsNeurotransmitter synthesisRegion-specific patternsOxidative metabolismDehydrogenase complex activityHippocampusStriatumEnergy metabolismCerebellumP30TCA cycle fluxP17P10Dependence of Oxygen Delivery on Blood Flow in Rat Brain: A 7 Tesla Nuclear Magnetic Resonance Study
Hyder F, Kennan R, Kida I, Mason G, Behar K, Rothman D. Dependence of Oxygen Delivery on Blood Flow in Rat Brain: A 7 Tesla Nuclear Magnetic Resonance Study. Cerebrovascular And Brain Metabolism Reviews 2000, 20: 485-498. PMID: 10724113, DOI: 10.1097/00004647-200003000-00007.Peer-Reviewed Original ResearchConceptsMagnetic resonance imagingCapillary bedOxygen deliveryML xCerebral oxygen deliveryNicotine hydrogen tartrateRespective control conditionsValues of CBFMorphine anesthesiaSensorimotor cortexForepaw stimulationSodium pentobarbitalRat brainBlood flowCMRO2Mature ratsCortical activityResonance imagingBasal conditionsPercentage changeRatsAdministrationCBF
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
15N-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
Oxidative Glucose Metabolism in Rat Brain During Single Forepaw Stimulation: A Spatially Localized 1H[13C] Nuclear Magnetic Resonance Study
Hyder F, Rothman* D, Mason† G, Rangarajan A, Behar‡ K, Shulman R. Oxidative Glucose Metabolism in Rat Brain During Single Forepaw Stimulation: A Spatially Localized 1H[13C] Nuclear Magnetic Resonance Study. Cerebrovascular And Brain Metabolism Reviews 1997, 17: 1040-1047. PMID: 9346428, DOI: 10.1097/00004647-199710000-00005.Peer-Reviewed Original ResearchIn 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
1994
Dynamic Magnetic Resonance Imaging of the Rat Brain during Forepaw Stimulation
Hyder F, Behar K, Martin M, Blamire A, Shulman R. Dynamic Magnetic Resonance Imaging of the Rat Brain during Forepaw Stimulation. Cerebrovascular And Brain Metabolism Reviews 1994, 14: 649-655. PMID: 8014212, DOI: 10.1038/jcbfm.1994.81.Peer-Reviewed Original ResearchConceptsSomatosensory areaChloralose-anesthetized ratsDynamic magnetic resonance imagingMagnetic resonance imagingForelimb motorForepaw stimulationRat brainBrain mapping methodsElectrical stimulationMR signal intensityParietal cortexResonance imagingBrain tissueCoronal planeFractional signal changeStimulationSignal changesOxygenation stateSignal intensityRatsAnteriorCortexBloodBrainMeasurement 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
1993
Characterization of macromolecule resonances in the 1H NMR spectrum of rat brain
Behar K, Ogino T. Characterization of macromolecule resonances in the 1H NMR spectrum of rat brain. Magnetic Resonance In Medicine 1993, 30: 38-44. PMID: 8371672, DOI: 10.1002/mrm.1910300107.Peer-Reviewed Original Research