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 ResearchTranslating Prefrontal Cortex Insights to the Clinic and Society
Rowe J, Datta D, Fiebach C, Jaeggi S, Liston C, Luna B, Rasmussen S, Roberts A, Sinha R, Haber S. Translating Prefrontal Cortex Insights to the Clinic and Society. 2024, 319-360. DOI: 10.7551/mitpress/15679.003.0019.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 riskThe 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 associationAn overview of preclinical models of traumatic brain injury (TBI): relevance to pathophysiological mechanisms
Fesharaki-Zadeh A, Datta D. An overview of preclinical models of traumatic brain injury (TBI): relevance to pathophysiological mechanisms. Frontiers In Cellular Neuroscience 2024, 18: 1371213. PMID: 38682091, PMCID: PMC11045909, DOI: 10.3389/fncel.2024.1371213.Peer-Reviewed Original ResearchClosed-Head Impact Model of Engineered Rotational AccelerationModel of traumatic brain injuryPreclinical modelsPreclinical models of traumatic brain injuryAnimal modelsTraumatic brain injuryControlled cortical impact injuryRodent preclinical modelsDisease modifying effectFluid percussion injuryCortical impact injuryBlast injuryAnimal models of traumatic brain injuryBrain injuryMotor vehicle accidentsTherapeutic regimenPathophysiological mechanismsEtiology of traumatic brain injuryPharmacological agentsSports related injuriesInjury modelCalcium dysregulationPrevalence of traumatic brain injuryClinical treatmentClinical settingβ1-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 Research
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 ResearchInterrogating the Etiology of Sporadic Alzheimer’s Disease Using Aging Rhesus Macaques: Cellular, Molecular, and Cortical Circuitry Perspectives
Datta D. Interrogating the Etiology of Sporadic Alzheimer’s Disease Using Aging Rhesus Macaques: Cellular, Molecular, and Cortical Circuitry Perspectives. The Journals Of Gerontology Series A 2023, 78: 1523-1534. PMID: 37279946, PMCID: PMC10460555, DOI: 10.1093/gerona/glad134.Peer-Reviewed Original ResearchConceptsPrimate dorsolateral prefrontal cortexSporadic Alzheimer's diseaseAlzheimer's diseaseDorsolateral prefrontal cortexRhesus macaquesPrefrontal cortexSignificant risk factorsHuman Alzheimer's diseaseAspartic acid (NMDA) receptorsNonhuman primate modelNovel therapeutic strategiesCalcium-buffering proteinsPattern of pathologyInflammatory cascadeTau pathologyNeuropathological cascadeSynaptic dysfunctionRisk factorsPrimate modelNeurofibrillary tanglesAmyloid plaquesDendritic spinesTherapeutic strategiesGenetic predispositionAnimal models557. 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. 557. Nanoscale Imaging of pT217-Tau in Aged Rhesus Macaque: Trans-Synaptic Propagation and Seeding of Tau Pathology in Entorhinal Cortex. Biological Psychiatry 2023, 93: s319. DOI: 10.1016/j.biopsych.2023.02.797.Peer-Reviewed Original Research
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 biomarkersP477. 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 factorEpigeneticsSimple, Single-Shot Phosphoproteomic Analysis of Heat-Stable Tau Identifies Age-Related Changes in pS235- and pS396-Tau Levels in Non-human Primates
Leslie SN, Kanyo J, Datta D, Wilson RS, Zeiss C, Duque A, Lam TT, Arnsten AFT, Nairn AC. Simple, Single-Shot Phosphoproteomic Analysis of Heat-Stable Tau Identifies Age-Related Changes in pS235- and pS396-Tau Levels in Non-human Primates. Frontiers In Aging Neuroscience 2021, 13: 767322. PMID: 34867294, PMCID: PMC8637411, DOI: 10.3389/fnagi.2021.767322.Peer-Reviewed Original ResearchTau phosphorylationPrefrontal cortexAlzheimer's diseaseAge-related changesLayer III pyramidal cellsRhesus monkey prefrontal cortexSignificant risk factorsMonkey prefrontal cortexNon-human primatesAD pathologyTau levelsRisk factorsPyramidal cellsRodent modelsIdentifies ageRhesus monkeysLiquid chromatography-tandem mass spectrometryTherapeutic developmentNatural aging processSignificant increaseTauAgeDiseaseRobust labelingMonkeysGlutamate Carboxypeptidase II in Aging Rat Prefrontal Cortex Impairs Working Memory Performance
Datta D, Leslie SN, Woo E, Amancharla N, Elmansy A, Lepe M, Mecca AP, Slusher BS, Nairn AC, Arnsten AFT. Glutamate Carboxypeptidase II in Aging Rat Prefrontal Cortex Impairs Working Memory Performance. Frontiers In Aging Neuroscience 2021, 13: 760270. PMID: 34867287, PMCID: PMC8634091, DOI: 10.3389/fnagi.2021.760270.Peer-Reviewed Original ResearchCognitive disordersRat medial PFCMedial PFCGCPII inhibitorsPFC cognitive deficitsPrefrontal cortical activationGlutamate carboxypeptidase IIGCPII proteinMGluR3 expressionLocal infusionSystemic administrationAged ratsGCPII inhibitionMemory performancePrefrontal cortex impairsCortical activationCognitive impairmentCognitive deficitsInflammationGenetic insultsCarboxypeptidase IIDisordersGCPIICurrent studyInhibitorsM1 receptors interacting with NMDAR enhance delay-related neuronal firing and improve working memory performance
Galvin VC, Yang S, Lowet AS, Datta D, Duque A, Arnsten AF, Wang M. M1 receptors interacting with NMDAR enhance delay-related neuronal firing and improve working memory performance. Current Research In Neurobiology 2021, 2: 100016. PMID: 35098156, PMCID: PMC8794314, DOI: 10.1016/j.crneur.2021.100016.Peer-Reviewed Original ResearchNicotinic α7 receptorsMemory performanceMemory taskNMDA receptorsSingle neuron activityMemory circuitryDLPFCPrimate dlPFCΑ7 receptorsM1 receptorsCognitive disordersDLPFC circuitryPermissive actionPersistent activityGlutamatergic NMDA receptorsNMDAR dysfunctionMemoryNMDAR blockadeMuscarinic M1 receptorsTreatment of schizophreniaRecurrent excitatory circuitsPositive allosteric modulatorsNMDA applicationExcitatory circuitsNeuronal activityStudies of aging nonhuman primates illuminate the etiology of early‐stage Alzheimer's‐like neuropathology: An evolutionary perspective
Arnsten AFT, Datta D, Preuss TM. Studies of aging nonhuman primates illuminate the etiology of early‐stage Alzheimer's‐like neuropathology: An evolutionary perspective. American Journal Of Primatology 2021, 83: e23254. PMID: 33960505, PMCID: PMC8550995, DOI: 10.1002/ajp.23254.Peer-Reviewed Original ResearchConceptsTau pathologyAssociation cortexAlzheimer's diseaseTau phosphorylationNMDAR-NR2BRhesus monkeysCognitive deficitsMonkey dorsolateral prefrontal cortexAlzheimer-like neuropathologyInternal calcium releaseGenetic mouse modelsDorsolateral prefrontal cortexSynaptic lossNeurofibrillary tanglesAmyloid plaquesMouse modelEarly molecular eventsSporadic formsAutosomal dominant formCalcium releasePerfusion fixationCortexPrefrontal cortexNonhuman primatesPathologySubcellular 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