2024
Proteomic Profile of Circulating Extracellular Vesicles in the Brain after Δ9-Tetrahydrocannabinol Inhalation
Lallai V, Lam T, Garcia-Milian R, Chen Y, Fowler J, Manca L, Piomelli D, Williams K, Nairn A, Fowler C. Proteomic Profile of Circulating Extracellular Vesicles in the Brain after Δ9-Tetrahydrocannabinol Inhalation. Biomolecules 2024, 14: 1143. PMID: 39334909, PMCID: PMC11430348, DOI: 10.3390/biom14091143.Peer-Reviewed Original ResearchConceptsImmediate early gene c-fosChronic THC exposureEarly gene c-fosCannabinoid 1 receptorGene c-fosSex-specific mannerTHC exposurePsychoactive componentExtracellular vesiclesCentral signaling mechanismDrug effectsTHCChoroid plexus epithelial cellsFemale ratsC-fosPlexus epithelial cellsBrainCannabisRelease of EVsRegulate intercellular communicationCerebrospinal fluidEpithelial cellsIntercellular signaling mediatorsEV signalingIntercellular communicationBERNN: Enhancing classification of Liquid Chromatography Mass Spectrometry data with batch effect removal neural networks
Pelletier S, Leclercq M, Roux-Dalvai F, de Geus M, Leslie S, Wang W, Lam T, Nairn A, Arnold S, Carlyle B, Precioso F, Droit A. BERNN: Enhancing classification of Liquid Chromatography Mass Spectrometry data with batch effect removal neural networks. Nature Communications 2024, 15: 3777. PMID: 38710683, PMCID: PMC11074280, DOI: 10.1038/s41467-024-48177-5.Peer-Reviewed Original ResearchConceptsLC-MS experimentsLC-MSLiquid chromatography mass spectrometry dataComplex biological samplesMass spectrometry dataLiquid chromatography mass spectrometryChromatography mass spectrometryMass spectrometrySpectrometry dataEffective removalBiological samplesExperimental conditionsBatch effect removalSample processing protocolBatch effectsSpectrometryBatch effect correction methodsCorrecting batch effectsRemoval of batch effectsOptimal conditions for carrying out trypsin digestions on complex proteomes: From bulk samples to single cells
Mansuri M, Bathla S, Lam T, Nairn A, Williams K. Optimal conditions for carrying out trypsin digestions on complex proteomes: From bulk samples to single cells. Journal Of Proteomics 2024, 297: 105109. PMID: 38325732, PMCID: PMC10939724, DOI: 10.1016/j.jprot.2024.105109.Peer-Reviewed Original ResearchComplex proteomesProtein cleavage activityOptimal conditionsTrypsin digestion protocolReversed phase HPLC separationMass spectrometry workflowMS-based proteomicsMass spectrometric analysisC-terminal amino acid residuesTrypsin digestionChromatographic separationDigestion protocolAmino acid residuesHPLC separationMS/MS analysisGlobal proteomic analysisSingle cellsSample matrixSpectrometric analysisCleavage specificityGeneration of peptidesAcid residuesDown proteinsProteomic analysisCleavage activity
2023
Mass spectrometry on cerebrospinal fluid uncovers association of novel glycolysis biomarkers with Alzheimer’s disease in a complex clinical cohort
de Geus M, Leslie S, Wang W, Lam T, Broekman M, Neefjes S, Nairn A, Carlyle B, Arnold S. Mass spectrometry on cerebrospinal fluid uncovers association of novel glycolysis biomarkers with Alzheimer’s disease in a complex clinical cohort. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.078466.Peer-Reviewed Original ResearchAlzheimer's diseaseMild cognitive impairmentHospital neurology serviceNon-AD diagnosesDiagnostic lumbar puncturePrognosis of ADCerebrospinal fluid biomarkersClinic cohortFurther mechanistic studiesNeurology serviceFDG-PETBrain metabolismFluid biomarkersLumbar puncturePatient cohortClinical indicationsDisease progressionATN biomarkersClinical cohortTreatment responseComplex cohortBackground DiagnosisCSF samplesTreatment efficacyLinear regression analysisMass spectrometry in cerebrospinal fluid uncovers association of glycolysis biomarkers with Alzheimer’s disease in a large clinical sample
de Geus M, Leslie S, Lam T, Wang W, Roux-Dalvai F, Droit A, Kivisakk P, Nairn A, Arnold S, Carlyle B. Mass spectrometry in cerebrospinal fluid uncovers association of glycolysis biomarkers with Alzheimer’s disease in a large clinical sample. Scientific Reports 2023, 13: 22406. PMID: 38104170, PMCID: PMC10725469, DOI: 10.1038/s41598-023-49440-3.Peer-Reviewed Original ResearchChronic 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 dysregulationOperant Training for Highly Palatable Food Alters Translating Messenger RNA in Nucleus Accumbens D2 Neurons and Reveals a Modulatory Role of Ncdn
Montalban E, Giralt A, Taing L, Nakamura Y, Pelosi A, Brown M, de Pins B, Valjent E, Martin M, Nairn A, Greengard P, Flajolet M, Hervé D, Gambardella N, Roussarie J, Girault J. Operant Training for Highly Palatable Food Alters Translating Messenger RNA in Nucleus Accumbens D2 Neurons and Reveals a Modulatory Role of Ncdn. Biological Psychiatry 2023, 95: 926-937. PMID: 37579933, PMCID: PMC11059129, DOI: 10.1016/j.biopsych.2023.08.006.Peer-Reviewed Original ResearchStriatal projection neuronsNucleus accumbensPalatable foodProjection neuronsNAc neuronsD2-striatal projection neuronsWild-type miceMessenger RNAConditioning-induced changesSpine densityDopamine neuronsDopamine receptorsDownregulated genesD2 neuronsModulatory roleNAc dopamineDopamine DFood altersCompensatory mechanismsRegular foodNeuronsFeeding behaviorBehavioral responsesMRNA alterationsMiceDifferential Effects of Cocaine and Morphine on the Diurnal Regulation of the Mouse Nucleus Accumbens Proteome
Ketchesin K, Becker-Krail D, Xue X, Wilson R, Lam T, Williams K, Nairn A, Tseng G, Logan R. Differential Effects of Cocaine and Morphine on the Diurnal Regulation of the Mouse Nucleus Accumbens Proteome. Journal Of Proteome Research 2023, 22: 2377-2390. PMID: 37311105, PMCID: PMC10392613, DOI: 10.1021/acs.jproteome.3c00126.Peer-Reviewed Original ResearchConceptsNucleus accumbensDiurnal regulationMouse nucleus accumbensPhase-dependent regulationBrain regionsDiurnal rhythmAdministration of psychostimulantsEffects of cocaineSubstance use disordersDifferential effectsMolecular rhythmsProtein rhythmsQuantitative proteomicsProteomic dataProteomeMorphine administrationUse of substancesRhythm alterationsGlucocorticoid signalingUse disordersMorphineSubstance useProtein expressionCocaineSignificant alterationsAdult-specific Reelin expression alters striatal neuronal organization: implications for neuropsychiatric disorders
Pardo M, Gregorio S, Montalban E, Pujadas L, Elias-Tersa A, Masachs N, Vílchez-Acosta A, Parent A, Auladell C, Girault J, Vila M, Nairn A, Manso Y, Soriano E. Adult-specific Reelin expression alters striatal neuronal organization: implications for neuropsychiatric disorders. Frontiers In Cellular Neuroscience 2023, 17: 1143319. PMID: 37153634, PMCID: PMC10157100, DOI: 10.3389/fncel.2023.1143319.Peer-Reviewed Original ResearchOverexpression of ReelinReelin levelsNeuropsychiatric disordersExtracellular matrix protein ReelinReelin expression levelsNigrostriatal dopaminergic projectionMedium spiny neuronsFunction mouse modelsHuman psychiatric disordersStriatal parvalbuminStriatal interneuronsStriatal patchesStriatal complexSpiny neuronsDopaminergic projectionsNeuronal compositionMouse modelProtein ReelinImmunohistochemical techniquesPsychiatric disordersBipolar disorderMice exhibitStriatal structuresAdult plasticityBrain developmentPeripheral signature of altered synaptic integrity in young onset cannabis use disorder: A proteomic study of circulating extracellular vesicles
Ganesh S, Lam T, Garcia-Milian R, D'Souza D, Nairn A, Elgert K, Eitan E, Ranganathan M. Peripheral signature of altered synaptic integrity in young onset cannabis use disorder: A proteomic study of circulating extracellular vesicles. The World Journal Of Biological Psychiatry 2023, 24: 603-613. PMID: 36994633, PMCID: PMC10471733, DOI: 10.1080/15622975.2023.2197039.Peer-Reviewed Original ResearchConceptsNeuron-derived extracellular vesiclesLabel-free quantification mass spectrometryProteomic studiesCannabis use disorderExtracellular vesiclesMass spectrometry proteomic analysisDifferential proteomic profilesAdapter proteinProteomic analysisPost-synaptic densityPeripheral signatureMolecular basisProteomic profilesProteinMarkers of neuropathologyBrain tissue samplesSynaptic pathologyVesiclesSynaptic integrityImmunoaffinity methodUse disordersFunctional integrityImportant insightsNeuropathologyPilot studyUncovering biology by single-cell proteomics
Mansuri M, Williams K, Nairn A. Uncovering biology by single-cell proteomics. Communications Biology 2023, 6: 381. PMID: 37031277, PMCID: PMC10082756, DOI: 10.1038/s42003-023-04635-2.Peer-Reviewed Original Research
2022
Applying Data‐Independent Acquisition Mass Spectrometry on Cerebrospinal Fluid Samples from a Neurology Clinic for Biomarker Discovery in Alzheimer’s Disease
de Geus M, Leslie S, Ramirez C, Trombetta B, Wang W, Lam T, Gotti C, Roux‐Dalvai F, Droit A, Nairn A, Arnold S, Carlyle B. Applying Data‐Independent Acquisition Mass Spectrometry on Cerebrospinal Fluid Samples from a Neurology Clinic for Biomarker Discovery in Alzheimer’s Disease. Alzheimer's & Dementia 2022, 18 DOI: 10.1002/alz.064314.Peer-Reviewed Original ResearchAlzheimer's diseaseMild cognitive impairmentPatient cohortAD-specific biomarkersNon-AD diagnosesPrognosis of ADCerebrospinal fluid samplesNeurology clinicBrain metabolismFluid biomarkersAD progressionCognitive prognosisComplex cohortBackground DiagnosisTreatment efficacyDementia diagnosisLarge-scale patient cohortsPathophysiological processesSpecific biomarkersRegulation of balanceDiagnosisCognitive AssessmentDiseaseCohortBiomarkersDiagnostic and Prognostic Performance of the Modified Lumipulse pTau 181 Assay in Plasma for Alzheimer’s Disease
Wilson E, Young C, Benitez J, Vandijck M, Swarovski M, Shahid M, Corso N, Kennedy G, Trelle A, Channappa D, Belnap M, Lind B, Le Bastard N, Quinn J, Nairn A, Kerchner G, Sha S, Wagner A, Henderson V, Longo F, Wyss‐Coray T, Poston K, Mormino E, Andreasson K. Diagnostic and Prognostic Performance of the Modified Lumipulse pTau 181 Assay in Plasma for Alzheimer’s Disease. Alzheimer's & Dementia 2022, 18 DOI: 10.1002/alz.060879.Peer-Reviewed Original ResearchAlzheimer's Disease Research CenterPtau-181Disease Research CenterAlzheimer's diseaseCohort 1Positron emission tomographyCohort 2Prognostic performanceAntibody combinationsAD participantsAβ42/Aβ40 ratioPreclinical Alzheimer's diseaseClinical AD diagnosisPlasma p-tau181Longitudinal cognitive declineTau pathologyAD pathologyCSF biomarkersTau-PETP-tau181Outcome measuresPhosphorylated tauPET biomarkersAβ40 ratioCognitive declinePerformance of a fully-automated Lumipulse plasma phospho-tau181 assay for Alzheimer’s disease
Wilson E, Young C, Ramos Benitez J, Swarovski M, Feinstein I, Vandijck M, Le Guen Y, Kasireddy N, Shahid M, Corso N, Wang Q, Kennedy G, Trelle A, Lind B, Channappa D, Belnap M, Ramirez V, Skylar-Scott I, Younes K, Yutsis M, Le Bastard N, Quinn J, van Dyck C, Nairn A, Fredericks C, Tian L, Kerchner G, Montine T, Sha S, Davidzon G, Henderson V, Longo F, Greicius M, Wagner A, Wyss-Coray T, Poston K, Mormino E, Andreasson K. Performance of a fully-automated Lumipulse plasma phospho-tau181 assay for Alzheimer’s disease. Alzheimer's Research & Therapy 2022, 14: 172. PMID: 36371232, PMCID: PMC9652927, DOI: 10.1186/s13195-022-01116-2.Peer-Reviewed Original ResearchConceptsPlasma p-tau181Alzheimer's Disease Research CenterP-tau181Disease Research CenterAlzheimer's diseasePositron emission tomographyAD dementiaBlood-based biomarker assaysAmyloid positron emission tomographyTreatment monitoringNovel blood-based biomarkersCSF p-tau181P-tau181 concentrationsDisease-modifying therapiesAβ42/Aβ40 ratioBlood-based biomarkersClinical AD diagnosisDetection of ADMild cognitive impairmentStudy cohortCSF biomarkersPlasma levelsAD groupPrognostic performanceCDR sumDARPP-32/protein phosphatase 1 regulates Rasgrp2 as a novel component of dopamine D1 receptor signaling in striatum
Kuroiwa M, Shuto T, Nagai T, Amano M, Kaibuchi K, Nairn A, Nishi A. DARPP-32/protein phosphatase 1 regulates Rasgrp2 as a novel component of dopamine D1 receptor signaling in striatum. Neurochemistry International 2022, 162: 105438. PMID: 36351540, DOI: 10.1016/j.neuint.2022.105438.Peer-Reviewed Original ResearchConceptsProtein phosphatase 1Phosphatase 1DARPP-32Receptor-induced phosphorylationPKA-dependent phosphorylationPKA/DARPPPP1 inhibitorPP1 substratesPP1 inhibitionPKA sitesRap1 activationOkadaic acidRASGRP2Novel componentRap1GAPPhosphorylationDARPP-32 knockout micePhospho-Thr34 DARPP-32Receptor activationPKAKnockout miceReceptor stimulationPP2A.Ser499Rap1Myosin light chain phosphatase catalytic subunit dephosphorylates cardiac myosin via mechanisms dependent and independent of the MYPT regulatory subunits
Lee E, Liu Z, Nguyen N, Nairn A, Chang AN. Myosin light chain phosphatase catalytic subunit dephosphorylates cardiac myosin via mechanisms dependent and independent of the MYPT regulatory subunits. Journal Of Biological Chemistry 2022, 298: 102296. PMID: 35872014, PMCID: PMC9418503, DOI: 10.1016/j.jbc.2022.102296.Peer-Reviewed Original ResearchConceptsMyosin light chain phosphataseRegulatory light chainRegulatory subunitCatalytic subunitPhosphatase catalytic subunitMain catalytic subunitSmooth muscle myosin light chain phosphataseNon-muscle cellsMuscle myosin light chain phosphataseMyosin regulatory light chainMyosin light chain kinaseLight chain kinasePP1cβTrimeric proteinConditional knockout miceLight chain phosphatasePhosphatase activitySubunitsPhosphate/Chain kinaseMuscle pathogenesisPhysiological regulationKnockout animalsMain isoformsProteinPP1cβ dephosphorylates cardiac myosin by MYPT‐dependent and independent mechanisms
Lee E, Liu Z, Nguyen N, Nairn A, Chang A. PP1cβ dephosphorylates cardiac myosin by MYPT‐dependent and independent mechanisms. The FASEB Journal 2022, 36 DOI: 10.1096/fasebj.2022.36.s1.r3877.Peer-Reviewed Original ResearchMyosin light chain phosphataseRegulatory light chainCardiac myosinSmooth muscleNormal cardiac functionMain catalytic subunitSmooth muscle contractionMyosin light chain kinaseMyosin phosphatase targetCardiac functionPP1cβLight chain kinaseCatalytic subunitAccessory subunitsConstitutive phosphorylationProtein stabilityLight chain phosphataseKnockout animalsMuscle contractionMuscle pathogenesisConditional knockoutCardiac muscle myosinCardiac myocytesCardiac musclePhosphatase activity
2021
Loss of Ftsj1 perturbs codon-specific translation efficiency in the brain and is associated with X-linked intellectual disability
Nagayoshi Y, Chujo T, Hirata S, Nakatsuka H, Chen C, Takakura M, Miyauchi K, Ikeuchi Y, Carlyle B, Kitchen R, Suzuki T, Katsuoka F, Yamamoto M, Goto Y, Tanaka M, Natsume K, Nairn A, Suzuki T, Tomizawa K, Wei F. Loss of Ftsj1 perturbs codon-specific translation efficiency in the brain and is associated with X-linked intellectual disability. Science Advances 2021, 7: eabf3072. PMID: 33771871, PMCID: PMC7997516, DOI: 10.1126/sciadv.abf3072.Peer-Reviewed Original ResearchTransfer RNAsTranslation efficiencyAberrant synaptic plasticityIntellectual disabilitySubset of genesPatient-derived cellsRibosome profilingKO miceSynaptic organizationSteady-state levelsKnockout miceMolecular pathogenesisSynaptic plasticityMemory deficitsSynaptic morphologyAnticodon regionPhe codonsBrainSlow decodingMechanistic insightsMiceFTSJ1GenesMethylationDisability
2020
Biochemical characterization of age‐related calcium‐cAMP‐PKA signaling dysregulation and its effect on tau pathology in rhesus monkey cortex
Leslie S, Datta D, Wang M, van Dyck C, Arnsten A, Nairn A. Biochemical characterization of age‐related calcium‐cAMP‐PKA signaling dysregulation and its effect on tau pathology in rhesus monkey cortex. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.042017.Peer-Reviewed Original ResearchTau pathologyAge-related dysregulationAlzheimer's diseaseIntracellular calciumTau phosphorylationRhesus monkeysRat primary cortical culturesHuman post-mortem samplesVulnerable brain regionsSporadic Alzheimer's diseaseAmyloid-beta plaquesPrimary cortical culturesMain pathological hallmarksRhesus monkey cortexTau neurofibrillary tanglesYears of ageEarly-onset formAge-related vulnerabilityDorsolateral prefrontal cortexAge-related changesMonkey DLPFCPost-mortem samplesAD pathologyAmyloid pathologyUnknown etiologyIdentification of NPTX2 as a prognostic biomarker of Alzheimer’s disease through a longitudinal CSF proteomics study in ADNI subjects
Libiger O, Shaw L, Watson M, Nairn A, Umaña K, Canet‐Avilés R, Jack C, Breton Y, Cortes L, Chelsky D, Spellman D, Baker S, Raghavan N, Potter W. Identification of NPTX2 as a prognostic biomarker of Alzheimer’s disease through a longitudinal CSF proteomics study in ADNI subjects. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.047605.Peer-Reviewed Original ResearchP-Tau 181Alzheimer's diseasePrognostic biomarkerRate of declineADNI subjectsLongitudinal changesTau-tangle pathologyBaseline clinical diagnosisAssociation of changesPre-specified analysis planMild cognitive impairmentTangle pathologyClinical progressionMixed-effects linear modelNegative subjectsClinical prognosisDisease continuumAdditional biomarkersAmyloid plaquesDrug development effortsNormal subjectsSubset of individualsRetrospective investigationBiomarker profilesPathologic processes