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 riskLateral expansion of the mammalian cerebral cortex is related to anchorage of centrosomes in apical neural progenitors
Morozov Y, Rakic P. Lateral expansion of the mammalian cerebral cortex is related to anchorage of centrosomes in apical neural progenitors. Cerebral Cortex 2024, 34: bhae293. PMID: 39024157, PMCID: PMC11485267, DOI: 10.1093/cercor/bhae293.Peer-Reviewed Original ResearchConceptsNeural progenitor cellsProgenitor cellsVentricular zoneCerebral cortexBasolateral cell membraneApical anchorageProlonged neurogenesisMammalian cerebral cortexPrimary ciliaApical neural progenitorsCell membraneFraction of cellsNeural progenitorsStem cellsCerebral neurogenesisApical segmentsDevelopment of ciliaNuclear translocationMicrotubule organizing centerNeurogenesisCellsMacaque monkeysSpecies-specific differencesCortexBasal bodiesNanoscale 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 biomarkersLocalization 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 signalingCalbindinDiseaseNeurons557. 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 ResearchDisorder of Golgi Apparatus Precedes Anoxia-Induced Pathology of Mitochondria
Morozov Y, Rakic P. Disorder of Golgi Apparatus Precedes Anoxia-Induced Pathology of Mitochondria. International Journal Of Molecular Sciences 2023, 24: 4432. PMID: 36901863, PMCID: PMC10003327, DOI: 10.3390/ijms24054432.Peer-Reviewed Original ResearchConceptsGolgi apparatusH anoxiaPost-translational protein modificationStomatin-like protein 2Role of mitochondriaEmbryonic mouse brainEmbryonic mouse brain cellsGolgi architectureSecretory traffickingMitochondrial matrixProtein modificationMouse brain cellsMitochondrial malfunctionTrans cisternaeBrain cellsMitochondriaOrganellesProtein 2Mitochondrial disordersLateral ganglionic eminenceEarly eventsComplex pathological changesMouse brainNormal ultrastructureGanglionic eminence
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
Subcellular 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
2020
The calcium‐containing smooth endoplasmic reticulum is a focus of risk factors for early‐ and late‐onset Alzheimer’s disease
Datta D, Mentone S, Morozov Y, van Dyck C, Arnsten A. The calcium‐containing smooth endoplasmic reticulum is a focus of risk factors for early‐ and late‐onset Alzheimer’s disease. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.047651.Peer-Reviewed Original ResearchLate-onset Alzheimer's diseaseAlzheimer's diseaseSmooth endoplasmic reticulumAD pathologyCalcium dysregulationRisk factorsCalcium leakMonkey dorsolateral prefrontal cortexAutosomal dominant Alzheimer's diseaseNeurofibrillary tangle formationGenetic risk factorsMedial temporal lobeDorsolateral prefrontal cortexMonkey DLPFCAD neurodegenerationTangle formationAge-related pathologiesTemporal lobeAnimal modelsAssociation cortexPS2 mutationTherapeutic interventionsBrain regionsEtiological eventInternal calciumCannabinoid Type 1 Receptor is Undetectable in Rodent and Primate Cerebral Neural Stem Cells but Participates in Radial Neuronal Migration
Morozov YM, Mackie K, Rakic P. Cannabinoid Type 1 Receptor is Undetectable in Rodent and Primate Cerebral Neural Stem Cells but Participates in Radial Neuronal Migration. International Journal Of Molecular Sciences 2020, 21: 8657. PMID: 33212822, PMCID: PMC7696736, DOI: 10.3390/ijms21228657.Peer-Reviewed Original ResearchConceptsNeural stem cellsStem cellsCannabinoid type 1 receptorType 1 receptorFate determinationRadial neuronal migrationCell movementEmbryonic developmentIntracellular vesiclesCellular locationMRNA sequencingMolecular mechanismsCortical plateElectron microscopic reconstructionCellular proliferationNeuronal migrationZone cellsSubventricular zone cellsEmbryonic miceMolecular substratesSVZ cellsMicroscopic reconstructionRecreational cannabis useMacaque cerebral cortexPrimate neuronsNeuron-Glia Inflammatory Interactions in Aging Rhesus Macaque Dorsolateral Prefrontal Cortex Layer III
Datta D, Morozov Y, Arnsten A. Neuron-Glia Inflammatory Interactions in Aging Rhesus Macaque Dorsolateral Prefrontal Cortex Layer III. Biological Psychiatry 2020, 87: s425. DOI: 10.1016/j.biopsych.2020.02.1084.Peer-Reviewed Original Research
2019
P4‐143: LOSS OF PDE4D REGULATION OF CAMP‐PKA‐CALCIUM SIGNALING IN THE AGING ASSOCIATION CORTEX: INCREASING RISK FOR LOAD
Datta D, Morozov Y, Arellano J, van Dyck C, Arnsten A. P4‐143: LOSS OF PDE4D REGULATION OF CAMP‐PKA‐CALCIUM SIGNALING IN THE AGING ASSOCIATION CORTEX: INCREASING RISK FOR LOAD. Alzheimer's & Dementia 2019, 15: p1329-p1329. DOI: 10.1016/j.jalz.2019.06.3804.Peer-Reviewed Original ResearchF164. Ultrastructural Localization of Classical Complement Cascade Signaling Protein C1q in Rhesus Macaque Dorsolateral Prefrontal Cortex
Datta D, Morozov Y, van Dyck C, Arnsten A. F164. Ultrastructural Localization of Classical Complement Cascade Signaling Protein C1q in Rhesus Macaque Dorsolateral Prefrontal Cortex. Biological Psychiatry 2019, 85: s276-s277. DOI: 10.1016/j.biopsych.2019.03.701.Peer-Reviewed Original Research
2017
[O2–02–03]: ULTRASTRUCTURAL EVIDENCE FOR IMPAIRED MITOCHONDRIAL FISSION IN THE AGED RHESUS MONKEY DORSOLATERAL PREFRONTAL CORTEX: RELEVANCE TO THE PATHOGENESIS OF ALZHEIMER's DISEASE
Datta D, Morozov Y, Paspalas A. [O2–02–03]: ULTRASTRUCTURAL EVIDENCE FOR IMPAIRED MITOCHONDRIAL FISSION IN THE AGED RHESUS MONKEY DORSOLATERAL PREFRONTAL CORTEX: RELEVANCE TO THE PATHOGENESIS OF ALZHEIMER's DISEASE. Alzheimer's & Dementia 2017, 13: p553-p553. DOI: 10.1016/j.jalz.2017.07.151.Peer-Reviewed Original ResearchM97. Impairments in Mitochondrial Fission in Rhesus Monkey Dorsolateral Prefrontal Cortex: Ultrastructural Evidence for a Novel Cellular Mechanism of Aging
Datta D, Morozov Y. M97. Impairments in Mitochondrial Fission in Rhesus Monkey Dorsolateral Prefrontal Cortex: Ultrastructural Evidence for a Novel Cellular Mechanism of Aging. Schizophrenia Bulletin 2017, 43: s246-s246. PMCID: PMC5475857, DOI: 10.1093/schbul/sbx022.092.Peer-Reviewed Original ResearchCannabinoid type 1 receptor-containing axons innervate NPY/AgRP neurons in the mouse arcuate nucleus
Morozov YM, Koch M, Rakic P, Horvath TL. Cannabinoid type 1 receptor-containing axons innervate NPY/AgRP neurons in the mouse arcuate nucleus. Molecular Metabolism 2017, 6: 374-381. PMID: 28377876, PMCID: PMC5369208, DOI: 10.1016/j.molmet.2017.01.004.Peer-Reviewed Original Research
2016
Ultrastructural evidence for impaired mitochondrial fission in the aged rhesus monkey dorsolateral prefrontal cortex
Morozov YM, Datta D, Paspalas CD, Arnsten AF. Ultrastructural evidence for impaired mitochondrial fission in the aged rhesus monkey dorsolateral prefrontal cortex. Neurobiology Of Aging 2016, 51: 9-18. PMID: 28027494, PMCID: PMC5292282, DOI: 10.1016/j.neurobiolaging.2016.12.001.Peer-Reviewed Original Research