2024
Characterizing the Most Vulnerable Prefrontal Cortical Neurons in Schizophrenia
Arnsten A, Datta D. Characterizing the Most Vulnerable Prefrontal Cortical Neurons in Schizophrenia. American Journal Of Psychiatry 2024, 181: 861-864. PMID: 39350618, DOI: 10.1176/appi.ajp.20240731.Peer-Reviewed Original ResearchKey Roles of CACNA1C/Cav1.2 and CALB1/Calbindin in Prefrontal Neurons Altered in Cognitive Disorders
Datta D, Yang S, Joyce M, Woo E, McCarroll S, Gonzalez-Burgos G, Perone I, Uchendu S, Ling E, Goldman M, Berretta S, Murray J, Morozov Y, Arellano J, Duque A, Rakic P, O’Dell R, van Dyck C, Lewis D, Wang M, Krienen F, Arnsten A. Key Roles of CACNA1C/Cav1.2 and CALB1/Calbindin in Prefrontal Neurons Altered in Cognitive Disorders. JAMA Psychiatry 2024, 81: 870-881. PMID: 38776078, PMCID: PMC11112502, DOI: 10.1001/jamapsychiatry.2024.1112.Peer-Reviewed Original ResearchDorsolateral prefrontal cortexPrefrontal cortexLayer III pyramidal cellsWorking memoryCognitive disordersNeuronal firingPrimate dorsolateral prefrontal cortexPyramidal cellsSpatial working memoryWorking memory performanceRisk of mental disordersCalcium-related proteinsReduced neuronal firingL-type calcium channel Cav1.2GluN2B-NMDA receptorsL-type calcium channel activityPrefrontal neuronsL-type calcium channel blockerMemory performanceL-type calcium channelsMental disordersRisk of cognitive disordersCognitive behaviorProtein expressionAssociated with increased riskStress and inflammation target dorsolateral prefrontal cortex function: Neural mechanisms underlying weakened cognitive control
Joyce M, Uchendu S, Arnsten A. Stress and inflammation target dorsolateral prefrontal cortex function: Neural mechanisms underlying weakened cognitive control. Biological Psychiatry 2024 PMID: 38944141, DOI: 10.1016/j.biopsych.2024.06.016.Peer-Reviewed Original ResearchMental disordersDorsolateral prefrontal cortex functionPrefrontal cortex functionSubgenual cingulate cortexRegulate emotional responsesDorsolateral prefrontal cortexChronic stress exposurePosterior association cortexMedial PFCCognitive controlPrefrontal cortexWorking memoryCingulate cortexRegulate attentionCortex functionNeural mechanismsDlPFCBrain regionsStress exposureAssociation cortexTop-down projectionsEmotional responsesSpine lossArousal statePersistent firingThe meso-connectomes of mouse, marmoset, and macaque: network organization and the emergence of higher cognition
Magrou L, Joyce M, Froudist-Walsh S, Datta D, Wang X, Martinez-Trujillo J, Arnsten A. The meso-connectomes of mouse, marmoset, and macaque: network organization and the emergence of higher cognition. Cerebral Cortex 2024, 34: bhae174. PMID: 38771244, PMCID: PMC11107384, DOI: 10.1093/cercor/bhae174.Peer-Reviewed Original ResearchConceptsInter-areal connectionsVisual cortexPrimary visual cortexHigher cortical areasMacaque cortexPrimate specializationHigher cognitionPrimate cortexV1Working memory storageDendritic spine densityTop-down regulationPrefrontal cortexConnection structureSpine densityFunctional segregationCortical areasFrontal areasCortexConnectomeNetwork organizationMemory storageMultimodal associationβ1-adrenoceptor expression on GABAergic interneurons in primate dorsolateral prefrontal cortex: potential role in stress-induced cognitive dysfunction
Joyce M, Yang S, Morin K, Duque A, Arellano J, Datta D, Wang M, Arnsten A. β1-adrenoceptor expression on GABAergic interneurons in primate dorsolateral prefrontal cortex: potential role in stress-induced cognitive dysfunction. Neurobiology Of Stress 2024, 30: 100628. PMID: 38550854, PMCID: PMC10973161, DOI: 10.1016/j.ynstr.2024.100628.Peer-Reviewed Original ResearchDorsolateral prefrontal cortexPrefrontal cortexStress-induced cognitive dysfunctionTreat stress-related disordersPrimate dorsolateral prefrontal cortexImpaired working memoryWorking memory deficitsWorking memory taskCalcium-binding proteins calbindinStress-related disordersClasses of inhibitory neuronsLevels of norepinephrineFast-spikingMemory taskDopamine releaseWorking memoryMemory deficitsInhibitory neuronsCognitive dysfunctionPV interneuronsGABAergic interneuronsDlPFCBehavior analysisCortexPyramidal cellsNanoscale imaging of pT217‐tau in aged rhesus macaque entorhinal and dorsolateral prefrontal cortex: Evidence of interneuronal trafficking and early‐stage neurodegeneration
Datta D, Perone I, Wijegunawardana D, Liang F, Morozov Y, Arellano J, Duque A, Xie Z, van Dyck C, Joyce M, Arnsten A. Nanoscale imaging of pT217‐tau in aged rhesus macaque entorhinal and dorsolateral prefrontal cortex: Evidence of interneuronal trafficking and early‐stage neurodegeneration. Alzheimer's & Dementia 2024, 20: 2843-2860. PMID: 38445818, PMCID: PMC11032534, DOI: 10.1002/alz.13737.Peer-Reviewed Original ResearchCombined Use of Guanfacine and N-Acetylcysteine for the Treatment of Cognitive Deficits After Traumatic Brain Injury
Khasnavis S, Belliveau T, Arnsten A, Fesharaki-Zadeh A. Combined Use of Guanfacine and N-Acetylcysteine for the Treatment of Cognitive Deficits After Traumatic Brain Injury. Neurotrauma Reports 2024, 5: 226-231. PMID: 38524728, PMCID: PMC10960163, DOI: 10.1089/neur.2023.0124.Peer-Reviewed Original ResearchTreatment of cognitive deficitsTraumatic brain injuryExecutive functionCognitive deficitsTraumatic brain injury clinicEfficacy of guanfacinePre-frontal cortexBrain injuryTreat traumatic brain injuryBehavioral therapyNeuropsychological testsCognitive symptomsCognitive changesPlacebo-controlled trialProcessing speedGuanfacineCortical functionOpen-label useApproved medicationsPersonsPost-treatmentDeficitsTraumatizationN-acetylcysteineMTBIDynamic Network Connectivity: from monkeys to humans
Arnsten A, Wang M, D’Esposito M. Dynamic Network Connectivity: from monkeys to humans. Frontiers In Human Neuroscience 2024, 18: 1353043. PMID: 38384333, PMCID: PMC10879414, DOI: 10.3389/fnhum.2024.1353043.Peer-Reviewed Original ResearchDynamic network connectivityFunctional MRIFunctional connectivityHuman brain imaging researchDorsolateral prefrontal cortexNMDA receptor neurotransmissionBrain imaging researchHuman fMRI studiesPrefrontal cortexReceptor neurotransmissionWorking memoryFMRI studyBrain regionsPersistent neuronal firingNeuromodulator acetylcholineCognitive disordersCortical regionsDlPFCPost-synaptic densityArousal stateStrength of synaptic connectionsNeuronal firingCognitive statesImaging researchDendritic spinesThe circuit mechanisms of working memory: Key roles of the dorsolateral prefrontal cortex
Arnsten A, Martinez-Trujillo J. The circuit mechanisms of working memory: Key roles of the dorsolateral prefrontal cortex. 2024 DOI: 10.1016/b978-0-443-15754-7.00038-9.Peer-Reviewed Original ResearchDorsolateral prefrontal cortexPrefrontal cortexWorking memoryMechanisms of working memorySpatial working memoryPosterior association cortexExecutive functionMediodorsal thalamusSketch padMental representationsAssociation cortexSubcortical connectionsCholinergic neurotransmissionCircuit mechanismsRecurrent excitatory circuitsNMDA receptorsAbstract thoughtPersistent firingPrimate researchCortexDlPFCExcitatory circuitsMemorySensory stimulationAlzheimer's diseaseInhibition of brain glutamate carboxypeptidase II (GCPII) to enhance cognitive function
Wiseman R, Bigos K, Arnsten A, Slusher B. Inhibition of brain glutamate carboxypeptidase II (GCPII) to enhance cognitive function. Advances In Pharmacology 2024 DOI: 10.1016/bs.apha.2024.10.018.Peer-Reviewed Original ResearchN-acetylaspartyl glutamateGlutamate carboxypeptidase IICognitive deficitsCognitive functionDorsolateral prefrontal cortex of primatesPrefrontal cortex of primatesHigher order cognitive processesDorsolateral prefrontal cortexMetabotropic glutamate receptor 3Inhibition of glutamate carboxypeptidase IIImprove cognitive deficitsEnhance cognitive functionImprove cognitive performanceEnzyme glutamate carboxypeptidase IIGlutamate receptor 3Executive functionCortex of primatesMGlu3 receptorsCarboxypeptidase IICognitive performanceCognitive processesPersistent neuronal firingClinical populationsNeuronal firingClinical work
2023
Anatomical characterization of pT217‐tau in aged rhesus macaque association cortices: Relevance for trans‐synaptic propagation in sporadic Alzheimer’s Disease
Datta D, Mentone S, Morozov Y, van Dyck C, Arnsten A. Anatomical characterization of pT217‐tau in aged rhesus macaque association cortices: Relevance for trans‐synaptic propagation in sporadic Alzheimer’s Disease. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.075998.Peer-Reviewed Original ResearchTau pathologyEntorhinal cortexAlzheimer's diseaseRhesus macaquesBrain tau pathologyHigher brain circuitsHigher cortical circuitsPattern of neurodegenerationAged rhesus macaquesHuman Alzheimer's diseaseSporadic Alzheimer's diseaseTrans-synaptic propagationSoluble tau speciesSequence of tauDorsolateral prefrontal cortexAmyloid pathologyExtracellular spaceDendritic shaftsAdvanced neurodegenerationTau hyperphosphorylationInhibitory synapsesNeurofibrillary tanglesGlutamatergic synapsesSpine apparatusAD biomarkersNanoscale imaging of pT217-tau in aged rhesus macaque: Trans-synaptic propagation and seeding of tau pathology in entorhinal cortex
Datta D, Arnsten A. Nanoscale imaging of pT217-tau in aged rhesus macaque: Trans-synaptic propagation and seeding of tau pathology in entorhinal cortex. Journal Of The Neurological Sciences 2023, 455: 122501. DOI: 10.1016/j.jns.2023.122501.Peer-Reviewed Original ResearchClinical experience with the α2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in “Long-COVID19”
Fesharaki-Zadeh A, Lowe N, Arnsten A. Clinical experience with the α2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in “Long-COVID19”. Neuroimmunology Reports 2023, 3: 100154. DOI: 10.1016/j.nerep.2022.100154.Peer-Reviewed Original ResearchN-acetylcysteineCognitive deficitsΑ2A-adrenoceptor agonistsPrefrontal cortexCOVID19 infectionPlacebo-controlled trialOpen-label treatmentCommon side effectsExecutive functionPFC connectionsBrain fogAcid blockadeLabel treatmentHypotensive episodesGuanfacine treatmentNMDA receptorsPatient brieflySide effectsClinical experienceGuanfacineCognitive impairmentPatientsPrefrontal connectivityDemonstrate efficacyPrefrontal function
2022
Nanoscale imaging of pT217‐tau in aged rhesus macaque: Trans‐synaptic propagation and seeding of tau pathology in entorhinal cortex
Datta D, Mentone S, Morozov Y, van Dyck C, Arnsten A. Nanoscale imaging of pT217‐tau in aged rhesus macaque: Trans‐synaptic propagation and seeding of tau pathology in entorhinal cortex. Alzheimer's & Dementia 2022, 18 DOI: 10.1002/alz.064956.Peer-Reviewed Original ResearchTau pathologyAlzheimer's diseaseEntorhinal cortexCerebrospinal fluidLayers IIRhesus macaquesBrain tau pathologyHigher brain circuitsHigher cortical circuitsPattern of neurodegenerationAged rhesus macaquesHuman Alzheimer's diseaseTrans-synaptic propagationSoluble tau speciesSequence of tauAmyloid pathologyExtracellular spaceDendritic shaftsTau hyperphosphorylationGlutamatergic synapsesInhibitory synapsesNeurofibrillary tanglesSpine apparatusAD biomarkersEarly biomarkersThe Aversive Lens: Stress effects on the prefrontal-cingulate cortical pathways that regulate emotion
Arnsten A, Joyce M, Roberts A. The Aversive Lens: Stress effects on the prefrontal-cingulate cortical pathways that regulate emotion. Neuroscience & Biobehavioral Reviews 2022, 145: 105000. PMID: 36529312, PMCID: PMC9898199, DOI: 10.1016/j.neubiorev.2022.105000.Peer-Reviewed Original ResearchConceptsCortical pathwaysStress exposureDendritic spine lossChronic stress exposureAnti-depressant treatmentDeep brain stimulationPrefrontal cortical areasExcessive dopamineNeuromodulatory treatmentSSRI medicationNorepinephrine releaseSpine lossSubgenual cingulateCortical areasBrain stimulationChronic stressBA25MedicationsDorsolateral PFCTreatmentExposurePsychic painPainKetamineSymptomsKappa opioid receptor antagonism protects working memory performance from mild stress exposure in Rhesus macaques
Wallace T, Martin W, Arnsten A. Kappa opioid receptor antagonism protects working memory performance from mild stress exposure in Rhesus macaques. Neurobiology Of Stress 2022, 21: 100493. PMID: 36532373, PMCID: PMC9755019, DOI: 10.1016/j.ynstr.2022.100493.Peer-Reviewed Original ResearchKappa-opioid receptorsKOR systemKappa opioid receptor antagonismNeurobehavioral disordersStress exposureSelective KOR antagonistOpioid receptor antagonismClinical evidence pointsBenzodiazepine inverse agonistStress-induced dysfunctionMild stress exposureKOR antagonistsReceptor antagonismMesocortical pathwayOpioid receptorsTherapeutic benefitKOR activityInverse agonistKOR expressionReceptor systemRhesus macaquesMild stress responseBrain networksEvidence pointsFunctional influenceP477. Anatomical Evaluation of Calcium-Related Schizophrenia Risk Genes in Rhesus Macaque Dorsolateral Prefrontal Cortex
Datta D, Mentone S, Morozov Y, Arnsten A. P477. Anatomical Evaluation of Calcium-Related Schizophrenia Risk Genes in Rhesus Macaque Dorsolateral Prefrontal Cortex. Biological Psychiatry 2022, 91: s281-s282. DOI: 10.1016/j.biopsych.2022.02.713.Peer-Reviewed Original ResearchSubcellular localization of PDE4D and HCN1 in rhesus macaque entorhinal cortex layer II: Signature of vulnerability in Alzheimer’s disease
Datta D, Mentone S, Morozov Y, van Dyck C, Arnsten A. Subcellular localization of PDE4D and HCN1 in rhesus macaque entorhinal cortex layer II: Signature of vulnerability in Alzheimer’s disease. Alzheimer's & Dementia 2022, 17 DOI: 10.1002/alz.054671.Peer-Reviewed Original ResearchEntorhinal cortex layer IICortex layer IILayers IIAlzheimer's diseaseTau pathologySmooth endoplasmic reticulumPostsynaptic compartmentsPrefrontal cortexLayer II cellsLayer II stellate cellsDisease courseAsymmetric synapsesGlutamatergic circuitsDendritic shaftsCalcium dysregulationGlutamatergic synapsesSpine apparatusExcitatory synapsesCalcium leakAD subjectsDendritic spinesStellate cellsAssociation cortexCalcium extrusionSynaptic strength
2021
PDE4D And HCN1 Ultrastructure In Rhesus Macaque Entorhinal Cortex: Relevance For Aging And Alzheimer's Disease
Datta D, Mentone S, Arnsten A. PDE4D And HCN1 Ultrastructure In Rhesus Macaque Entorhinal Cortex: Relevance For Aging And Alzheimer's Disease. Innovation In Aging 2021, 5: 638-639. PMCID: PMC8681434, DOI: 10.1093/geroni/igab046.2410.Peer-Reviewed Original ResearchDNA CpG methylationProtein mass spectrometrySomatic mutationsAge-related molecular changesSimilar genetic backgroundEpigenetic regulatorsCpG methylationEpigenetic alterationsWhole-exome sequencingMolecular damageGenetic backgroundDNAmeMolecular changesPostmortem brain samplesBrain samplesAbstract AgingSame brain samplesAlzheimer's diseaseCurrent understandingBiological agingBinding propertiesMutationsMass spectrometryMajor risk factorEpigeneticsSubcellular Localization of Schizophrenia Risk Genes Encoding Cav1.2 (CACNA1C) and VIPR2 in Rhesus Macaque Dorsolateral Prefrontal Cortex
Datta D, Mentone S, Morozov Y, Arnsten A. Subcellular Localization of Schizophrenia Risk Genes Encoding Cav1.2 (CACNA1C) and VIPR2 in Rhesus Macaque Dorsolateral Prefrontal Cortex. Biological Psychiatry 2021, 89: s308. DOI: 10.1016/j.biopsych.2021.02.768.Peer-Reviewed Original Research