2024
Key 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 riskNanoscale 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
Chronic GCPII (glutamate‐carboxypeptidase‐II) inhibition reduces pT217Tau levels in the entorhinal and dorsolateral prefrontal cortices of aged macaques
Bathla S, Datta D, Liang F, Barthelemy N, Wiseman R, Slusher B, Asher J, Zeiss C, Ekanayake‐Alper D, Holden D, Terwilliger G, Duque A, Arellano J, van Dyck C, Bateman R, Xie Z, Nairn A, Arnsten A. Chronic GCPII (glutamate‐carboxypeptidase‐II) inhibition reduces pT217Tau levels in the entorhinal and dorsolateral prefrontal cortices of aged macaques. Alzheimer's & Dementia: Translational Research & Clinical Interventions 2023, 9: e12431. PMID: 37915375, PMCID: PMC10617575, DOI: 10.1002/trc2.12431.Peer-Reviewed Original ResearchSporadic Alzheimer's diseaseEntorhinal cortexGCPII inhibitionDorsolateral prefrontal cortexChronic inhibitionTau pathologyTau hyperphosphorylationAged macaquesType 3 metabotropic glutamate receptorAlzheimer's diseasePrefrontal cortexRhesus macaquesVehicle-treated monkeysAged rhesus macaquesMetabotropic glutamate receptorsApparent side effectsAmyloid beta 1Regulation of calciumGCPII inhibitorsKey etiological factorGCPII activityPrimate dlPFCNeuronal damageCSF analysisCalcium dysregulationLocalization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer’s disease
Datta D, Perone I, Morozov Y, Arellano J, Duque A, Rakic P, van Dyck C, Arnsten A. Localization of PDE4D, HCN1 channels, and mGluR3 in rhesus macaque entorhinal cortex may confer vulnerability in Alzheimer’s disease. Cerebral Cortex 2023, 33: 11501-11516. PMID: 37874022, PMCID: PMC10724870, DOI: 10.1093/cercor/bhad382.Peer-Reviewed Original ResearchConceptsHCN1 channelsTau pathologyGlutamate synapsesEntorhinal cortexCalcium actionInternal calcium releaseEntorhinal cortex stellate cellsDorsolateral prefrontal cortexSusceptible neuronsInitial pathologySelective vulnerabilityEtiological factorsTau phosphorylationStellate cellsAlzheimer's diseaseSpecific neuronsCalcium releasePrefrontal cortexCortexSynapse strengthPathologyCalcium signalingCalbindinDiseaseNeurons
2022
Subcellular 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
Age‐related calcium dysregulation linked with tau pathology and impaired cognition in non‐human primates
Datta D, Leslie SN, Wang M, Morozov YM, Yang S, Mentone S, Zeiss C, Duque A, Rakic P, Horvath TL, van Dyck C, Nairn AC, Arnsten AFT. Age‐related calcium dysregulation linked with tau pathology and impaired cognition in non‐human primates. Alzheimer's & Dementia 2021, 17: 920-932. PMID: 33829643, PMCID: PMC8195842, DOI: 10.1002/alz.12325.Peer-Reviewed Original ResearchConceptsTau pathologyCalcium leakTau phosphorylationNeuronal firingAlzheimer's diseaseEarly tau phosphorylationPyramidal cell dendritesSporadic Alzheimer's diseasePrimary cortical neuronsPotential therapeutic targetCognitive performanceAge-related reductionMacaque dorsolateral prefrontal cortexDorsolateral prefrontal cortexNon-human primatesCalcium dysregulationCell dendritesCortical neuronsCalcium-binding proteinsAD biomarkersPathology markersTherapeutic targetAnimal modelsAged monkeysPrefrontal cortex
2020
Neurobiologic Rationale for Treatment of Apathy in Alzheimer's Disease With Methylphenidate
van Dyck CH, Arnsten AFT, Padala PR, Brawman-Mintzer O, Lerner AJ, Porsteinsson AP, Scherer RW, Levey AI, Herrmann N, Jamil N, Mintzer JE, Lanctôt KL, Rosenberg PB. Neurobiologic Rationale for Treatment of Apathy in Alzheimer's Disease With Methylphenidate. American Journal Of Geriatric Psychiatry 2020, 29: 51-62. PMID: 32461027, PMCID: PMC7641967, DOI: 10.1016/j.jagp.2020.04.026.Peer-Reviewed Original ResearchConceptsTreatment of apathyAlzheimer's diseaseCortical-basal ganglia circuitsPrefrontal cortexMotivated behaviorPublic health burdenSymptoms of apathyCatecholaminergic treatmentNeurobiologic rationaleNeuropsychiatric symptomsDopamine actionGanglia circuitsHealth burdenThalamocortical circuitsCognitive symptomsMethylphenidate actionsCatecholamine actionNeuronal circuitsSymptomsDiseaseApathetic behaviorTreatmentInitial trialMethylphenidateAD results
2017
The aged rhesus macaque manifests Braak stage III/IV Alzheimer's‐like pathology
Paspalas CD, Carlyle BC, Leslie S, Preuss TM, Crimins JL, Huttner AJ, van Dyck C, Rosene DL, Nairn AC, Arnsten AFT. The aged rhesus macaque manifests Braak stage III/IV Alzheimer's‐like pathology. Alzheimer's & Dementia 2017, 14: 680-691. PMID: 29241829, PMCID: PMC6178089, DOI: 10.1016/j.jalz.2017.11.005.Peer-Reviewed Original ResearchConceptsLate-onset Alzheimer's diseaseCortical pathologyEntorhinal cortexAnimal modelsBraak stage III/IVAlzheimer's diseaseStage III/IVRhesus macaquesProgression of tauAlzheimer-like pathologyPrimary visual cortexSequence of tauDorsolateral prefrontal cortexTau pathologyPreventive strategiesAssociation cortexVisual cortexPrefrontal cortexCortexPathologyDiseaseOld animalsProtein kinase A (PKA) phosphorylationGenetic insultsMacaques
2000
The Alpha-2A-Adrenoceptor Agonist, Guanfacine, Increases Regional Cerebral Blood Flow in Dorsolateral Prefrontal Cortex of Monkeys Performing a Spatial Working Memory Task
Avery R, Franowicz J, Studholme C, van Dyck C, Arnsten A. The Alpha-2A-Adrenoceptor Agonist, Guanfacine, Increases Regional Cerebral Blood Flow in Dorsolateral Prefrontal Cortex of Monkeys Performing a Spatial Working Memory Task. Neuropsychopharmacology 2000, 23: 240-249. PMID: 10942848, DOI: 10.1016/s0893-133x(00)00111-1.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic alpha-2 Receptor AgonistsAdrenergic alpha-AgonistsAnimalsCerebrovascular CirculationCognitionFemaleGuanfacineImage Processing, Computer-AssistedMacaca mulattaMagnetic Resonance ImagingMemoryPrefrontal CortexSpace PerceptionStimulation, ChemicalTomography, Emission-Computed, Single-PhotonConceptsRegional cerebral blood flowCerebral blood flowPrefrontal cortexDorsolateral prefrontal cortexBlood flowAlpha 2A-adrenoceptorsAuditory association areasSuperior temporal cortexBlood flow tracerSPECT measuresAdrenoceptor agonistsAdrenoceptor stimulationAlpha-2aMemory taskAdrenoreceptor agonistIntravenous cathetersGuanfacine treatmentTemporal cortexRCBF valuesAssociation areasBrain regionsGuanfacineCortexSpatial Working Memory taskCognitive performance