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
2014
cAMP-PKA phosphorylation of tau confers risk for degeneration in aging association cortex
Carlyle BC, Nairn AC, Wang M, Yang Y, Jin LE, Simen AA, Ramos BP, Bordner KA, Craft GE, Davies P, Pletikos M, Šestan N, Arnsten AF, Paspalas CD. cAMP-PKA phosphorylation of tau confers risk for degeneration in aging association cortex. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 5036-5041. PMID: 24707050, PMCID: PMC3977284, DOI: 10.1073/pnas.1322360111.Peer-Reviewed Original ResearchConceptsNeurofibrillary tanglesAssociation cortexAlzheimer's diseaseSpine apparatusPhosphorylated tauPattern of neurodegenerationLate-stage diseaseHigh-risk factorsNormal aged miceGenetic rodent modelsPrefrontal association cortexPrimary sensory cortexPrimary visual cortexAge-related increasePyramidal neuronsCorticocortical connectionsAged miceRisk factorsGlutamate synapsesSpine synapsesSelective vulnerabilityRodent modelsDendritic spinesSensory cortexProtein kinase phosphorylation
2010
Dynamic Network Connectivity: A new form of neuroplasticity
Arnsten AF, Paspalas CD, Gamo NJ, Yang Y, Wang M. Dynamic Network Connectivity: A new form of neuroplasticity. Trends In Cognitive Sciences 2010, 14: 365-375. PMID: 20554470, PMCID: PMC2914830, DOI: 10.1016/j.tics.2010.05.003.Peer-Reviewed Original Research
1997
The Alpha-1 Adrenergic Agonist, Cirazoline, Impairs Spatial Working Memory Performance in Aged Monkeys
Arnsten A, Jentsch JD. The Alpha-1 Adrenergic Agonist, Cirazoline, Impairs Spatial Working Memory Performance in Aged Monkeys. Pharmacology Biochemistry And Behavior 1997, 58: 55-59. PMID: 9264070, DOI: 10.1016/s0091-3057(96)00477-7.Peer-Reviewed Original ResearchConceptsAlpha-1 adrenergic agonistAdrenergic antagonistsAdrenergic agonistsAlpha-1 adrenergic antagonistAlpha-1 adrenergic receptorsAdditional high affinityGood brain penetranceAlpha 2 receptorsAdrenergic receptor stimulationPrefrontal cortical functionSpatial Working Memory PerformanceBrain penetranceImidazoline receptorsCortical functionNonspecific changesCirazolineControl trialMemory performanceReceptor stimulationAdrenergic receptorsLow dosesRhesus monkeysAged monkeysPrefrontal cortexDrug actionThe effects of 5-HT3 receptor antagonists on cognitive performance in aged monkeys
Arnsten A, Lin C, Van Dyck C, Stanhope K. The effects of 5-HT3 receptor antagonists on cognitive performance in aged monkeys. Neurobiology Of Aging 1997, 18: 21-28. PMID: 8983029, DOI: 10.1016/s0197-4580(96)00162-5.Peer-Reviewed Original ResearchConceptsVisual object discriminationObject discriminationFine motor tasksMotor tasksCognitive-enhancing effectsMemory taskResponse taskCognitive performanceReceptor antagonistEnhanced acquisitionCognitive functionReliable improvementMarmoset researchAged monkeysTaskReversal conditionsWide dose rangeDiscriminationSide effectsLow dosesRhesus monkeysDose rangeAntagonistAcquisitionMonkeysNoradrenergic Influences on Prefrontal Cortical Cognitive Function: Opposing Actions at Postjunctional α1 Versus α2-Adrenergic Receptors
Arnsten A, Steere JC, Jentsch DJ, Li BM. Noradrenergic Influences on Prefrontal Cortical Cognitive Function: Opposing Actions at Postjunctional α1 Versus α2-Adrenergic Receptors. Advances In Pharmacology 1997, 42: 764-767. PMID: 9328010, DOI: 10.1016/s1054-3589(08)60859-5.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPrefrontal cortexNE releaseΑ2 receptorsCognitive impairmentBeneficial effectsPFC functionBasal NE releasePrefrontal cortical cognitive functionΑ2-adrenergic receptorsCortical cognitive functionsPotential cognitive enhancersAttention deficit hyperactivity disorderMemory functionDeficit hyperactivity disorderPostsynaptic α1Α1d subtypesNE terminalsΑ-adrenoceptorsΑ2 agonistsLithium medicationNoradrenergic influenceOpen trialLithium pretreatmentΑ2A subtypeΑ2A receptors
1995
Dopamine D2 receptor mechanisms contribute to age-related cognitive decline: the effects of quinpirole on memory and motor performance in monkeys
Arnsten A, Cai J, Steere J, Goldman-Rakic P. Dopamine D2 receptor mechanisms contribute to age-related cognitive decline: the effects of quinpirole on memory and motor performance in monkeys. Journal Of Neuroscience 1995, 15: 3429-3439. PMID: 7751922, PMCID: PMC6578230, DOI: 10.1523/jneurosci.15-05-03429.1995.Peer-Reviewed Original ResearchConceptsYoung adult monkeysFine motor tasksFine motor performanceAge-related cognitive declineAdult monkeysCognitive declineMotor performanceAged monkeysD2 dopamine receptor agonistDopamine D2 receptor mechanismsMotor tasksAged monkey brainsD2 receptor mechanismsDopamine receptor agonistsPrefrontal cortical cognitive functionEffects of quinpiroleD2 receptor functionCortical cognitive functionsAge-related lossDelayed response performanceQuinpirole responseDA depletionMotor cortexD2 autoreceptorsPostsynaptic receptors
1993
Postsynaptic alpha-2 receptor stimulation improves memory in aged monkeys: Indirect effects of yohimbine versus direct effects of clonidine
Arnsten A, Cai JX. Postsynaptic alpha-2 receptor stimulation improves memory in aged monkeys: Indirect effects of yohimbine versus direct effects of clonidine. Neurobiology Of Aging 1993, 14: 597-603. PMID: 7905189, DOI: 10.1016/0197-4580(93)90044-c.Peer-Reviewed Original ResearchConceptsPostsynaptic alpha-2 adrenoceptorsPostsynaptic alpha-2 receptorsAlpha-2 adrenoceptorsAlpha 2 receptorsAged monkeysAged animalsAlpha-2 receptor stimulationAlpha-2 adrenergic antagonistBeneficial effectsAlpha-2 antagonistAlpha-2 agonistsCognitive-enhancing effectsNE systemClonidine actsNE releaseAdrenergic antagonistsYohimbine treatmentReceptor stimulationLow dosesClonidineYohimbineNorepinephrineBeneficial dosesYoung monkeysMonkeysCatecholamine mechanisms in age-related cognitive decline
Arnsten A. Catecholamine mechanisms in age-related cognitive decline. Neurobiology Of Aging 1993, 14: 639-641. PMID: 7905190, DOI: 10.1016/0197-4580(93)90054-f.Peer-Reviewed Original Research
1990
Analysis of alpha-2 adrenergic agonist effects on the delayed nonmatch-to-sample performance of aged rhesus monkeys
Arnsten A, Goldman-Rakic PS. Analysis of alpha-2 adrenergic agonist effects on the delayed nonmatch-to-sample performance of aged rhesus monkeys. Neurobiology Of Aging 1990, 11: 583-590. PMID: 1980719, DOI: 10.1016/0197-4580(90)90021-q.Peer-Reviewed Original Research
1988
The alpha-2 adrenergic agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects: evidence for alpha-2 receptor subtypes
Arnsten A, Cai J, Goldman-Rakic P. The alpha-2 adrenergic agonist guanfacine improves memory in aged monkeys without sedative or hypotensive side effects: evidence for alpha-2 receptor subtypes. Journal Of Neuroscience 1988, 8: 4287-4298. PMID: 2903226, PMCID: PMC6569464, DOI: 10.1523/jneurosci.08-11-04287.1988.Peer-Reviewed Original ResearchConceptsAlpha-2 receptor subtypesB-HT920Alpha-2 agonistsReceptor subtypesRank order potencyLow dosesDose-response profilesBlood pressureSide effectsHigh dosesAlpha-2 adrenergic agonistsOrder potencyHypotensive side effectsSedative side effectsSubtypes of receptorsAged nonhuman primatesAged rhesus monkeysMemory-enhancing effectsMemory-impairing effectsClonidine effectAgonist guanfacineClonidineAdrenergic agonistsGuanfacineSedation
1985
α2-Adrenergic Mechanisms in Prefrontal Cortex Associated with Cognitive Decline in Aged Nonhuman Primates
Arnsten A, Goldman-Rakic P. α2-Adrenergic Mechanisms in Prefrontal Cortex Associated with Cognitive Decline in Aged Nonhuman Primates. Science 1985, 230: 1273-1276. PMID: 2999977, DOI: 10.1126/science.2999977.Peer-Reviewed Original ResearchConceptsBeneficial effectsAlpha-adrenergic systemReceptor agonist clonidineAlpha 2 receptorsΑ2-adrenergic mechanismsAged nonhuman primatesDorsolateral prefrontal cortexAgonist clonidineSite of actionAged humansPharmacological profileAged nonhumanCognitive declineCognitive deficitsCognitive functionPrefrontal cortexDrug actionNonhuman primatesMemory disordersClonidineLesionsCortex