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 ResearchMeSH KeywordsAnimalsGamma-Aminobutyric AcidGlucoseGlutamic AcidHumansMagnetic Resonance SpectroscopyModels, BiologicalNeurogliaOxidation-ReductionSensitivity and SpecificityConceptsGamma-amino butyric acid (GABA) neuronsNeuronal glucose oxidationGlutamate-glutamine cyclingRelease of lactateGlucose oxidationNeuronal oxidationGlial uptakeGABAergic neuronsGlutamate uptakeGliaNeuronsGlycolytic ATPLactateGlucoseTotal glucoseVivo rateIsoelectricityCulture studiesATPNeurotransmittersUptakeEvidence 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
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 compositionRatsCortexInhibition
1999
New NMR measurements in epilepsy. Measuring brain GABA in patients with complex partial seizures.
Petroff O, Behar K, Rothman D. New NMR measurements in epilepsy. Measuring brain GABA in patients with complex partial seizures. Advances In Neurology 1999, 79: 939-45. PMID: 10514877.Peer-Reviewed Original Research
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 spectroscopyControlNeuromodulatorsNeuronsDoseDoses
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 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 ResearchMeSH KeywordsAdultAnticonvulsantsEpilepsy, Complex PartialFemaleGamma-Aminobutyric AcidHumansMaleMiddle AgedOccipital LobeSeizuresSpectrum AnalysisTime FactorsVigabatrinConceptsBrain 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 concentrationHuman brain GABA levels rise rapidly after initiation of vigabatrin therapy
Petroff O, Rothman D, Behar K, Collins T, Mattson R. Human brain GABA levels rise rapidly after initiation of vigabatrin therapy. Neurology 1996, 47: 1567-1571.. PMID: 8960747, DOI: 10.1212/wnl.47.6.1567.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAnticonvulsantsBrainEpilepsyGamma-Aminobutyric AcidHumansMagnetic Resonance SpectroscopyVigabatrinConceptsBrain GABA levelsBrain GABASingle oral doseOral doseGABA levelsSide effectsHuman brain GABA levelsEffective antiepileptic medicationsHours of administrationAntiepileptic medicationsVigabatrin therapyDay dosingIntractable epilepsySerial measurementsOccipital cortexVigabatrinDay 8Day 5GABAGABA transaminasePatientsDoseNext dayHuman brainMagnetic resonance spectroscopyHuman 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 ResearchThe effect of gabapentin on brain gamma‐aminobutyric acid in patients with epilepsy
Petroff O, Rothman D, Behar K, Lamoureux D, Mattson R. The effect of gabapentin on brain gamma‐aminobutyric acid in patients with epilepsy. Annals Of Neurology 1996, 39: 95-99. PMID: 8572673, DOI: 10.1002/ana.410390114.Peer-Reviewed Original ResearchConceptsGamma-aminobutyric acidBrain GABA levelsGABA levelsHuman brain GABA levelsBrain gamma-aminobutyric acidHigh-dose gabapentinAntiepileptic drug treatmentEffect of gabapentinPartial epilepsy patientsTreatment of epilepsyMechanism of actionAdjunctive therapyStandard dosesDrug treatmentEpilepsy patientsOccipital cortexGabapentinPatientsClinical useEpilepsyHuman brainMagnetic resonanceTreatmentMagnetic resonance spectroscopyVivo measurements
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 observationsMedicationsCerebrumLevelsDoseVigabatrin: effect on brain GABA levels measured by nuclear magnetic resonance spectroscopy
Mattson R, Petroff O, Rothman D, Behar K. Vigabatrin: effect on brain GABA levels measured by nuclear magnetic resonance spectroscopy. Acta Neurologica Scandinavica. Supplementum 1995, 92: 27-30. PMID: 7495186, DOI: 10.1111/j.1600-0404.1995.tb00496.x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsBrain GABA levelsGABA levelsBrain concentrationsNerve terminalsAdministration of vigabatrinClear dose-response relationshipLevels of GABAPartial epileptic seizuresAnti-epilepsy drugsPresynaptic nerve terminalsDose-response relationshipConcentration of GABASecondary generalizationClinical effectsClinical outcomesVigabatrin administrationClinical trialsPatient responseClinical studiesSynaptic transmissionBaseline valuesOptimal doseVigabatrin levelsVigabatrinEpileptic seizures
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
1993
Localized 1H NMR measurements of gamma-aminobutyric acid in human brain in vivo.
Rothman D, Petroff O, Behar K, Mattson R. Localized 1H NMR measurements of gamma-aminobutyric acid in human brain in vivo. Proceedings Of The National Academy Of Sciences Of The United States Of America 1993, 90: 5662-5666. PMID: 8516315, PMCID: PMC46781, DOI: 10.1073/pnas.90.12.5662.Peer-Reviewed Original ResearchConceptsGamma-aminobutyric acidGABA concentrationGABA-transaminase inhibitor vigabatrinBrain gamma-aminobutyric acidDose-dependent elevationSeizure suppressionOccipital lobeHigh doseNonepileptic subjectsHuman volunteersHuman cortexVigabatrinDrug vigabatrinBrainPatientsHuman brainVolunteersCortexDose