2025
Frontal noradrenergic and cholinergic transients exhibit distinct spatiotemporal dynamics during competitive decision-making
Wang H, Ortega H, Kelly E, Indajang J, Savalia N, Glaeser-Khan S, Feng J, Li Y, Kaye A, Kwan A. Frontal noradrenergic and cholinergic transients exhibit distinct spatiotemporal dynamics during competitive decision-making. Science Advances 2025, 11: eadr9916. PMID: 40138407, PMCID: PMC11939063, DOI: 10.1126/sciadv.adr9916.Peer-Reviewed Original ResearchConceptsNeuromodulatory signalsCompetitive decision-makingCholinergic transientsNE signalingPremotor cortexAnimal's propensityBehavioral correlatesAcetylcholine signalingMatching pennies gamePattern of NEBehavioral eventsNorepinephrineCortexDecision-makingAcetylcholinePremotorFunctional relevanceOptogenetics
2024
Spatiotemporal Organization of Prefrontal Norepinephrine Influences Neuronal Activity
Glaeser-Khan S, Savalia N, Cressy J, Feng J, Li Y, Kwan A, Kaye A. Spatiotemporal Organization of Prefrontal Norepinephrine Influences Neuronal Activity. ENeuro 2024, 11: eneuro.0252-23.2024. PMID: 38702188, PMCID: PMC11134306, DOI: 10.1523/eneuro.0252-23.2024.Peer-Reviewed Original ResearchTwo-photon imagingLocus coeruleusPrefrontal cortexOptical flow analysisIn vivo two-photon imagingInfluence neuronal activityVesicle exocytosisControl of cortical activityNE releaseGPCR-based sensorsNE dynamicsLocal fieldNeuronal calciumNeuronal firingCell firingNE roleNorepinephrineHomogeneous fieldNeuronal activitySpatiotemporal activity patternsNeurotransmitter functionSensorLight-sheet imagingAxonal dynamicsSpatial scalesFrontal Norepinephrine Represents a Threat Prediction Error Under Uncertainty
Basu A, Yang J, Yu A, Glaeser-Khan S, Rondeau J, Feng J, Krystal J, Li Y, Kaye A. Frontal Norepinephrine Represents a Threat Prediction Error Under Uncertainty. Biological Psychiatry 2024, 96: 256-267. PMID: 38316333, PMCID: PMC11269024, DOI: 10.1016/j.biopsych.2024.01.025.Peer-Reviewed Original ResearchPrediction error signalsResponses to conditioned stimuliThreat prediction errorsReinforcement learning modelThreat learningAnticipation of dangerAversive learningMemory strengthConditioned stimulusNoradrenergic signalingDefensive behaviorError signalPrediction errorAuditory stimuliTask structureNorepinephrine releaseNorepinephrineLearning modelsPredictive signalsStimuliFootshockDopamineLearningRewardError
2022
Associations of neurotransmitters and the gut microbiome with emotional distress in mixed type of irritable bowel syndrome
Barandouzi Z, Lee J, del Carmen Rosas M, Chen J, Henderson W, Starkweather A, Cong X. Associations of neurotransmitters and the gut microbiome with emotional distress in mixed type of irritable bowel syndrome. Scientific Reports 2022, 12: 1648. PMID: 35102266, PMCID: PMC8803858, DOI: 10.1038/s41598-022-05756-0.Peer-Reviewed Original ResearchConceptsEmotional distressNeurotransmitter levelsHealthy controlsIrritable bowel syndrome groupIrritable bowel syndromeRegulation of neurotransmittersDepressive symptomsSerotonin levelsGut-brain axisEmotional symptomsHC groupPlasma neurotransmittersDistressGut microbiome profilesNeurotransmitterGut microbiomeNorepinephrine levelsBowel syndromeMicrobiome profilesPersonsNorepinephrineNested Case-Control StudySymptomsCase-control studySerotoninChapter 4 The adrenal glands
Holt E, Lupsa B, Lee G, Bassyouni H, Peery H. Chapter 4 The adrenal glands. 2022, 101-143. DOI: 10.1016/b978-0-12-815844-9.00004-x.Chapters
2021
Food odors decrease longevity via a brain–gut axis
Price K, Nitabach M. Food odors decrease longevity via a brain–gut axis. Nature Aging 2021, 1: 237-238. PMID: 37118407, DOI: 10.1038/s43587-021-00047-1.Peer-Reviewed Original Research
2018
Job-related burnout is associated with brain neurotransmitter levels in Chinese medical workers: a cross-sectional study
Yao Y, Zhao S, Zhang Y, Tang L, An Z, Lu L, Yao S. Job-related burnout is associated with brain neurotransmitter levels in Chinese medical workers: a cross-sectional study. Journal Of International Medical Research 2018, 46: 3226-3235. PMID: 29808771, PMCID: PMC6134687, DOI: 10.1177/0300060518775003.Peer-Reviewed Original ResearchConceptsNeurotransmitter levelsMedical staffCerebral cortexMaslach Burnout Inventory-General SurveyJob-related burnoutBrain neurotransmitter levelsLevels of neurotransmittersCross-sectional studyNeurotransmitter γ-aminobutyric acidΓ-aminobutyric acidPsychiatric disordersNorepinephrineChinese medical workersMedical workersDopamineCortexOccupational burnoutPresent studySexSignificant interactionStaffExhaustionLow levelsModerate levelsLevels
2015
Preclinical to Clinical Translation of CNS Transporter Occupancy of TD-9855, a Novel Norepinephrine and Serotonin Reuptake Inhibitor
Smith J, Patil D, Daniels O, Ding YS, Gallezot JD, Henry S, Kim K, Kshirsagar S, Martin W, Obedencio G, Stangeland E, Tsuruda P, Williams W, Carson R, Patil. Preclinical to Clinical Translation of CNS Transporter Occupancy of TD-9855, a Novel Norepinephrine and Serotonin Reuptake Inhibitor. The International Journal Of Neuropsychopharmacology 2015, 18: pyu027. PMID: 25522383, PMCID: PMC4368888, DOI: 10.1093/ijnp/pyu027.Peer-Reviewed Original ResearchMeSH KeywordsAdultAniline CompoundsAnimalsBlood Chemical AnalysisBrainHalf-LifeHumansMagnetic Resonance ImagingMaleModels, BiologicalMorpholinesNeurotransmitter Uptake InhibitorsNorepinephrine Plasma Membrane Transport ProteinsPhenyl EthersPiperidinesPositron-Emission TomographyRadiopharmaceuticalsRats, Sprague-DawleyReboxetineSerotonin Plasma Membrane Transport ProteinsSpinal CordSulfidesConceptsReuptake inhibitorsPositron emission tomographyNorepinephrine transporterSerotonin transporterSerotonin reuptake inhibitorsSingle oral doseUnique clinical profileMonoamine reuptake inhibitorsFuture clinical evaluationRat spinal cordNET occupancySERT occupancyClinical profileOral dosePlasma levelsTransporter profilesClinical evaluationSpinal cordTransporter occupancyCNS penetrationHealthy malesPharmacodynamic modelingNorepinephrineEmission tomographyPET studies
2014
Human iPSC Neurons Display Activity-Dependent Neurotransmitter Secretion: Aberrant Catecholamine Levels in Schizophrenia Neurons
Hook V, Brennand K, Kim Y, Toneff T, Funkelstein L, Lee K, Ziegler M, Gage F. Human iPSC Neurons Display Activity-Dependent Neurotransmitter Secretion: Aberrant Catecholamine Levels in Schizophrenia Neurons. Stem Cell Reports 2014, 3: 531-538. PMID: 25358781, PMCID: PMC4223699, DOI: 10.1016/j.stemcr.2014.08.001.Peer-Reviewed Original ResearchConceptsHiPSC neuronsHuman-induced pluripotent stem cell-derived neuronsPluripotent stem cell-derived neuronsActivity-dependent secretionStem cell-derived neuronsCell-derived neuronsPositive neuronsCatecholamine levelsActivity-dependent mannerTyrosine hydroxylasePeptide neurotransmittersNeuronal culturesBrain disordersNeurotransmitter releaseChemical neurotransmissionKCl stimulationNeuronsNorepinephrineCatecholaminesElevated levelsNeurotransmitter secretionCatecholamine biosynthesisSchizophreniaDopamineNeurotransmitters
2012
Renalase Lowers Ambulatory Blood Pressure by Metabolizing Circulating Adrenaline
Desir GV, Tang L, Wang P, Li G, Sampaio‐Maia B, Quelhas‐Santos J, Pestana M, Velazquez H. Renalase Lowers Ambulatory Blood Pressure by Metabolizing Circulating Adrenaline. Journal Of The American Heart Association 2012, 1: e002634. PMID: 23130169, PMCID: PMC3487338, DOI: 10.1161/jaha.112.002634.Peer-Reviewed Original ResearchSympathetic nervous systemBlood pressureHypotensive effectNervous systemAmbulatory blood pressureTreatment of hypertensionBlood pressure regulationNovel therapeutic modalitiesPlasma epinephrineVasoactive hormonesRecombinant renalaseCardiac diseaseSystemic pressureTherapeutic modalitiesVivo administrationDopamine precursorΑ-methyldopaPressure regulationRenalaseEpinephrineSingle nucleotide polymorphismsHypertensionNorepinephrineUnique small moleculesSingle amino acid mutation
2008
Multi‐scale modeling of neuronal adaptation mediated by angiotensin II in the central regulation of blood pressure
Vadigepalli R, Nikolaev E, Miller G, Ogunnaike B, Gonye G, Kholodenko B, Schwaber J. Multi‐scale modeling of neuronal adaptation mediated by angiotensin II in the central regulation of blood pressure. The FASEB Journal 2008, 22: 756.2-756.2. DOI: 10.1096/fasebj.22.1_supplement.756.2.Peer-Reviewed Original ResearchRelease of norepinephrineAngiotensin II receptorsSynthesis of norepinephrineType 1 activationAP-1PI3K pathwayCardiorespiratory neuronsBlood pressureAngiotensin IIC-Jun activationCardiovascular regulationCNS neuronsLong-term effectsCentral regulationTyrosine hydroxylaseTranscription factor AP-1Rate-limiting enzymeII receptorsKey neurotransmitterNeuronal adaptationFactor AP-1NorepinephrineK pathwayC-fos
2007
Modulation of angiotensin II and norepinephrine-induced plasminogen activator inhibitor-1 expression by AT1a receptor deficiency
Brown NJ, Bradford J, Wang Z, Lea W, Ma L, Ma J, Vaughan DE, Fogo AB. Modulation of angiotensin II and norepinephrine-induced plasminogen activator inhibitor-1 expression by AT1a receptor deficiency. Kidney International 2007, 72: 72-81. PMID: 17429342, DOI: 10.1038/sj.ki.5002268.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IIAngiotensin II Type 1 Receptor BlockersAnimalsAortaBlood PressureGene Expression RegulationKidneyLiverLosartanMaleMiceMice, Inbred C57BLMice, KnockoutMyocardiumNorepinephrinePlasminogen Activator Inhibitor 1Random AllocationReceptor, Angiotensin, Type 1RNA, MessengerVasoconstrictor AgentsConceptsPAI-1 expressionPlasminogen activator inhibitor-1 expressionSystolic blood pressureAng IIBlood pressureReceptor deficiencyWT miceAngiotensin IIBaseline systolic blood pressureAT1a receptor deficiencyEffects of losartanReceptor knockout micePressor responseWT heartsReceptor mRNAKnockout miceLosartanNorepinephrinePAI-1AortaKidneyLiverMiceCell-type specificHeartNorepinephrine and cognitive disorders
Arnsten A. Norepinephrine and cognitive disorders. 2007, 408-435. DOI: 10.1017/cbo9780511544156.015.Peer-Reviewed Original ResearchNoradrenergic drugsCentral nervous system norepinephrineNervous system norepinephrineRole of norepinephrineNoradrenergic neuronsCNS diseaseTherapeutic effectCognitive disordersNorepinephrineNeurological disordersNorepinephrine's roleBrain diseasesNew disease indicationsChemical neurotransmittersDisease indicationsDrugsDiseasePharmacologyDisordersTherapeuticsBasic biologyMolecular biologyNeurotransmittersNeuronsBrain
2004
Changes in cerebrospinal fluid neurochemistry during pregnancy
Altemus M, Fong J, Yang R, Damast S, Luine V, Ferguson D. Changes in cerebrospinal fluid neurochemistry during pregnancy. Biological Psychiatry 2004, 56: 386-392. PMID: 15364035, DOI: 10.1016/j.biopsych.2004.06.002.Peer-Reviewed Original ResearchConceptsPregnant womenCerebrospinal fluidCSF prolactinElective cesarean sectionHealthy nonpregnant womenCerebrospinal fluid neurochemistryLevels of prolactinCesarean sectionNonpregnant womenBrain GABACSF levelsNeurohormonal systemsBrain neurotransmittersCSF glutamateHomovanillic acidPregnancyBrain functionProlactinWomenPlasma samplesCSF oxytocinAminobutyric acidAlters regulationAnxietyNorepinephrine
2002
Hypocretin/Orexin Excites Hypocretin Neurons via a Local Glutamate Neuron—A Potential Mechanism for Orchestrating the Hypothalamic Arousal System
Li Y, Gao X, Sakurai T, van den Pol AN. Hypocretin/Orexin Excites Hypocretin Neurons via a Local Glutamate Neuron—A Potential Mechanism for Orchestrating the Hypothalamic Arousal System. Neuron 2002, 36: 1169-1181. PMID: 12495630, DOI: 10.1016/s0896-6273(02)01132-7.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAnimalsArousalCarrier ProteinsExcitatory Amino Acid AgonistsFeedbackGABA Agonistsgamma-Aminobutyric AcidGenes, ReporterGlutamic AcidGreen Fluorescent ProteinsHypothalamusImmunohistochemistryIntracellular Signaling Peptides and ProteinsLuminescent ProteinsMiceMice, TransgenicNeural InhibitionNeural PathwaysNeuronsNeuropeptidesOrexinsPresynaptic TerminalsSodium Channel BlockersSynaptic TransmissionConceptsHypothalamic arousal systemsHypocretin neuronsArousal systemSpike frequencyLocal glutamatergic neuronsMouse brain slicesGlutamate releaseGlutamatergic neuronsHypocretin-1Hypocretin cellsPresynaptic facilitationBrain slicesNeuron activityOutward currentsEnergy homeostasisModulates sleepNeuronsPotential mechanismsDirect effectPossible mechanismCellsNarcolepsyHypocretinNorepinephrineAcetylcholine
2001
Intravenous cocaine increases plasma epinephrine and norepinephrine in humans
Sofuoglu M, Nelson D, Babb D, Hatsukami D. Intravenous cocaine increases plasma epinephrine and norepinephrine in humans. Pharmacology Biochemistry And Behavior 2001, 68: 455-459. PMID: 11325399, DOI: 10.1016/s0091-3057(01)00482-8.Peer-Reviewed Original ResearchConceptsNorepinephrine concentrationsPlasma epinephrineHeart rate changesBlood pressureCocaine injectionHuman studiesPeak plasma epinephrineSympathoadrenal system activationPlacebo-controlled studyDiastolic blood pressureSystolic blood pressureDose of cocaineMale cocaine usersPlasma norepinephrineEpinephrine levelsSympathoadrenal systemCocaine administrationIntravenous injectionSystem activationIntravenous cocaineEpinephrineConsecutive daysNorepinephrineCocaineCocaine users
2000
Introduction
Arnsten A. Introduction. 2000, 73-75. DOI: 10.1093/oso/9780195133714.003.0003.Peer-Reviewed Original ResearchGenetics of Childhood Disorders: XVIII. ADHD, Part 2: Norepinephrine Has a Critical Modulatory Influence on Prefrontal Cortical Function
ARNSTEN A, Lombroso P. Genetics of Childhood Disorders: XVIII. ADHD, Part 2: Norepinephrine Has a Critical Modulatory Influence on Prefrontal Cortical Function. Journal Of The American Academy Of Child & Adolescent Psychiatry 2000, 39: 1201-1203. PMID: 10986819, DOI: 10.1097/00004583-200009000-00022.Peer-Reviewed Original ResearchConceptsPrefrontal cortical functionCortical functionModulatory influenceChildhood disordersNorepinephrine
1999
Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder
Southwick S, Bremner J, Rasmusson A, Morgan C, Arnsten A, Charney D. Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder. Biological Psychiatry 1999, 46: 1192-1204. PMID: 10560025, DOI: 10.1016/s0006-3223(99)00219-x.Peer-Reviewed Original ResearchConceptsRole of norepinephrineClinical studiesNorepinephrine's roleTrauma-related alterationsRe-experiencing symptomsFear-provoking stimuliTreatment of PTSDPosttraumatic stress disorderChronic uncontrollable stressPharmacologic treatmentClinical findingsNeuronal reactivityIntrusive memoriesAdrenergic blockersEnhanced encodingSelective attentionPreclinical studiesReceptor sensitivityAversive eventsNorepinephrineTraumatic stressNovel stimuliStress disorderMAO inhibitorsUncontrollable stress
1997
Addition of desipramine to serotonin reuptake inhibitors in treatment- resistant obsessive-compulsive disorder
Barr LC, Goodman WK, Anand A, McDougle CJ, Price LH. Addition of desipramine to serotonin reuptake inhibitors in treatment- resistant obsessive-compulsive disorder. American Journal Of Psychiatry 1997, 154: 1293-1295. PMID: 9286191, DOI: 10.1176/ajp.154.9.1293.Peer-Reviewed Original ResearchConceptsSelective serotonin reuptake inhibitorsReuptake inhibitorsObsessive-compulsive disorderObsessive-compulsive symptomsTreatment-resistant obsessive-compulsive disorderDouble-blind studyNorepinephrine reuptake inhibitorsReuptake of norepinephrineSerotonin reuptake inhibitorsAddition of desipraminePlacebo groupSuperior efficacyDepressive symptomsDesipramineSymptomsSignificant differencesPatientsTreatmentInhibitorsDisordersPlaceboNorepinephrineClomipramineReuptakeWeeks
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