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 ResearchDecrease 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 fluxP17P10
1999
Determination 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
Vigabatrin increases human brain homocarnosine and improves seizure control
Petroff O, Mattson R, Behar K, Hyder F, Rothman D. Vigabatrin increases human brain homocarnosine and improves seizure control. Annals Of Neurology 1998, 44: 948-952. PMID: 9851440, DOI: 10.1002/ana.410440614.Peer-Reviewed Original ResearchConceptsGamma-aminobutyric acidSeizure controlGABA concentrationAddition of vigabatrinLow-dose vigabatrinImproved seizure controlMean GABA concentrationAntiepileptic drug vigabatrinInhibitory neuromodulatorDaily doseGABAergic neuronsGABA levelsLarge dosesHomocarnosine concentrationsVigabatrinDrug vigabatrinHomocarnosinePatientsHuman brainMagnetic resonance spectroscopyControlNeuromodulatorsNeuronsDoseDoses15N-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
Homocarnosine and the measurement of neuronal pH in patients with epilepsy
Rothman D, Behar K, Prichard J, Petroff O. Homocarnosine and the measurement of neuronal pH in patients with epilepsy. Magnetic Resonance In Medicine 1997, 38: 924-929. PMID: 9402193, DOI: 10.1002/mrm.1910380611.Peer-Reviewed Original ResearchOxidative 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
1996
Human Brain γ‐Aminobutyric Acid Levels and Seizure Control Following Initiation of Vigabatrin Therapy
Petroff O, Behar K, Mattson R, Rothman D. Human Brain γ‐Aminobutyric Acid Levels and Seizure Control Following Initiation of Vigabatrin Therapy. Journal Of Neurochemistry 1996, 67: 2399-2404. PMID: 8931472, DOI: 10.1046/j.1471-4159.1996.67062399.x.Peer-Reviewed Original ResearchConceptsBrain GABA contentImproved seizure controlBrain GABA levelsSeizure controlVigabatrin treatmentGABA levelsDaily doseAntiepileptic drugsOccipital lobeBrain gamma-aminobutyric acid (GABA) concentrationsGABA concentrationHuman brain GABA levelsGABA contentGamma-aminobutyric acid concentrationΓ-aminobutyric acid (GABA) levelsComplex partial seizuresNovel antiepileptic drugBrain GABA concentrationsSeizure frequencyPartial seizuresVigabatrin therapySustained elevationHuman occipital lobeGABA synthesisAcid levelsLow brain GABA level is associated with poor seizure control
Petroff O, Rothman D, Behar K, Mattson R. Low brain GABA level is associated with poor seizure control. Annals Of Neurology 1996, 40: 908-911. PMID: 9007096, DOI: 10.1002/ana.410400613.Peer-Reviewed Original ResearchConceptsLower GABA levelsBrain GABA levelsLower brain GABA levelsPoor seizure controlGABA levelsSeizure controlRecent seizuresGamma-aminobutyric acid concentrationComplex partial seizuresPartial seizuresEpileptic syndromesEpileptic focusOccipital lobeCerebrospinal fluidPatientsSeizuresSignificant associationMagnetic resonanceVivo measurementsSurface coilLevelsEpilepsySyndromeGABAAcid concentrationShort echo time proton magnetic resonance spectroscopic imaging of macromolecule and metabolite signal intensities in the human brain
Hwang J, Graham G, Behar K, Alger J, Prichard J, Rothman D. Short echo time proton magnetic resonance spectroscopic imaging of macromolecule and metabolite signal intensities in the human brain. Magnetic Resonance In Medicine 1996, 35: 633-639. PMID: 8722812, DOI: 10.1002/mrm.1910350502.Peer-Reviewed Original ResearchConceptsSubacute stroke patientsProton magnetic resonance spectroscopicProton magnetic resonance spectroscopic imagingMagnetic resonance spectroscopic imagingStroke patientsHealthy subjectsMagnetic resonance spectroscopicMetabolite signal intensitiesBrain regionsPathological conditionsMacromolecule resonancesHuman brainBrainSignal intensitySubjectsRecovery timeSpectroscopic imagingPatientsHuman brain GABA levels rise after initiation of vigabatrin therapy but fail to rise further with increasing dose
Petroff O, Rothman D, Behar K, Mattson R. Human brain GABA levels rise after initiation of vigabatrin therapy but fail to rise further with increasing dose. Neurology 1996, 46: 1459-1463. PMID: 8628502, DOI: 10.1212/wnl.46.5.1459.Peer-Reviewed Original Research