2024
Repetitive Mild Closed-Head Injury Induced Synapse Loss and Increased Local BOLD-fMRI Signal Homogeneity
Markicevic M, Mandino F, Toyonaga T, Cai Z, Fesharaki-Zadeh A, Shen X, Strittmatter S, Lake E. Repetitive Mild Closed-Head Injury Induced Synapse Loss and Increased Local BOLD-fMRI Signal Homogeneity. Journal Of Neurotrauma 2024 PMID: 39096127, DOI: 10.1089/neu.2024.0095.Peer-Reviewed Original ResearchChronic variable stressRegional homogeneityFunctional brain abnormalitiesSynapse densityMild closed-head injuryClosed-head injuryTraumatic brain injuryTreat traumatic brain injuryNeurobiological alterationsMild head injuryVariable stressBrain abnormalitiesPositron emission tomographyMultimodal studiesSynaptic densityMagnetic resonance imagingBrain imagingBrain injuryInduce synapse lossFMRIInjured miceMouse modelEmission tomographyResonance imagingCompensatory mechanismsCharacterizing the Effects of Progranulin Reduction on Tau Pathology and Phenotypes in a Mouse Model of Tauopathy (P4-9.016)
Bhagwagar S, Takahashi H, Strittmatter S. Characterizing the Effects of Progranulin Reduction on Tau Pathology and Phenotypes in a Mouse Model of Tauopathy (P4-9.016). Neurology 2024, 102 DOI: 10.1212/wnl.0000000000205227.Peer-Reviewed Original Research
2023
Decreased synaptic vesicle glycoprotein 2A binding in a rodent model of familial Alzheimer's disease detected by [18F]SDM-16
Zheng C, Toyonaga T, Chen B, Nicholson L, Mennie W, Liu M, Spurrier J, Deluca K, Strittmatter S, Carson R, Huang Y, Cai Z. Decreased synaptic vesicle glycoprotein 2A binding in a rodent model of familial Alzheimer's disease detected by [18F]SDM-16. Frontiers In Neurology 2023, 14: 1045644. PMID: 36846134, PMCID: PMC9945093, DOI: 10.3389/fneur.2023.1045644.Peer-Reviewed Original ResearchStandardized uptake value ratioDistribution volume ratioAlzheimer's diseaseSimplified reference tissue modelSynapse lossMouse modelAPP/PS1 miceAge-matched wild-type miceAPPswe/PS1dE9 mouse modelAPP/PS1 AD mouse modelSlow brain kineticsAD mouse modelSynaptic vesicle glycoprotein 2APseudo-reference regionWild-type miceUptake value ratioMonths of ageDifferent brain regionsDifferent imaging windowsFamilial Alzheimer's diseasePET imaging studiesReference tissue modelPS1 miceBrain stemBrain kineticsPrion Protein Complex with mGluR5 Mediates Amyloid-ß Synaptic Loss in Alzheimer’s Disease
Roseman G, Fu L, Strittmatter S. Prion Protein Complex with mGluR5 Mediates Amyloid-ß Synaptic Loss in Alzheimer’s Disease. 2023, 467-481. DOI: 10.1007/978-3-031-20565-1_22.ChaptersAlzheimer's diseaseMouse modelAD transgenic mouse modelLong-term potentiation impairmentPrimary histopathological featureAD mouse modelAmyloid-beta plaquesTransgenic mouse modelPotential therapeutic targetSynaptic lossHistopathological featuresAD pathophysiologyNeuronal dysfunctionSynapse densityCognitive dysfunctionNeurofibrillary tanglesTherapeutic targetMemory deficitsCellular prion proteinMGluR5DiseaseCell death characteristicCommon formSynaptotoxicityDysfunction
2022
IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses
Clement M, Forbester J, Marsden M, Sabberwal P, Sommerville M, Wellington D, Dimonte S, Clare S, Harcourt K, Yin Z, Nobre L, Antrobus R, Jin B, Chen M, Makvandi-Nejad S, Lindborg J, Strittmatter S, Weekes M, Stanton R, Dong T, Humphreys I. IFITM3 restricts virus-induced inflammatory cytokine production by limiting Nogo-B mediated TLR responses. Nature Communications 2022, 13: 5294. PMID: 36075894, PMCID: PMC9454482, DOI: 10.1038/s41467-022-32587-4.Peer-Reviewed Original ResearchConceptsInterferon-induced transmembrane protein 3IL-6 productionViral pathogenesisCytokine productionPro-inflammatory cytokine productionInflammatory cytokine productionInflammatory cytokine responseSARS-CoV-2Transmembrane protein 3Dendritic cellsCytokine responsesImmunoregulatory pathwaysImmunoregulatory functionsTLR2 responsesTLR responsesMouse modelMyeloid cellsViral stimulationProtein 3PathogenesisRestriction factorsNogoCellular localizationResponseCellsReversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q
Spurrier J, Nicholson L, Fang XT, Stoner AJ, Toyonaga T, Holden D, Siegert TR, Laird W, Allnutt MA, Chiasseu M, Brody AH, Takahashi H, Nies SH, Pérez-Cañamás A, Sadasivam P, Lee S, Li S, Zhang L, Huang YH, Carson RE, Cai Z, Strittmatter SM. Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q. Science Translational Medicine 2022, 14: eabi8593. PMID: 35648810, PMCID: PMC9554345, DOI: 10.1126/scitranslmed.abi8593.Peer-Reviewed Original ResearchConceptsPositron emission tomographySilent allosteric modulatorsAlzheimer's diseaseMouse modelPhospho-tau accumulationAged mouse modelAlzheimer mouse modelImmune-mediated attackSAM treatmentMicroglial mediatorsSynaptic engulfmentSynaptic lossAD miceComplement component C1qSynapse lossGlutamate responseSynaptic densityDrug washoutSynaptic localizationTherapeutic benefitCognitive impairmentAllosteric modulatorsEmission tomographyNonhuman primatesComponent C1qAlzheimer risk gene product Pyk2 suppresses tau phosphorylation and phenotypic effects of tauopathy
Brody AH, Nies SH, Guan F, Smith LM, Mukherjee B, Salazar SA, Lee S, Lam TKT, Strittmatter SM. Alzheimer risk gene product Pyk2 suppresses tau phosphorylation and phenotypic effects of tauopathy. Molecular Neurodegeneration 2022, 17: 32. PMID: 35501917, PMCID: PMC9063299, DOI: 10.1186/s13024-022-00526-y.Peer-Reviewed Original ResearchConceptsPS19 miceTau phosphorylationDisease riskPyk2 expressionPyk2 activityHuman neuronal culturesAlzheimer's disease riskNeuro-inflammationSynapse lossTau accumulationTau pathologyMouse survivalC1q depositionT cellsAssociated pathologyMouse modelLittermate controlsMAPK activityHuman neuronsHuman tauNeuronal culturesPyk2 inhibitionVivo modelMouse brainSynaptic function
2020
Elucidating the role of the AD risk factor Pyk2 in tau‐induced neuronal dysfunction
Brody A, Strittmatter S. Elucidating the role of the AD risk factor Pyk2 in tau‐induced neuronal dysfunction. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.036625.Peer-Reviewed Original ResearchSpatial memory impairmentCell layer thicknessGenetic deletionTau pathologyTau phosphorylationMemory impairmentPharmacological inhibitionAcute hippocampal slice preparationsTau-induced neuronal dysfunctionHippocampal slice preparationPS19 miceNeuronal dysfunctionSlice preparationHistological assessmentMouse modelKnockout micePyk2 activityExacerbationMicePyk2PathologyImpairmentAnimalsTauPhenotypeQuantification of SV2A Binding in Rodent Brain Using [18F]SynVesT-1 and PET Imaging
Sadasivam P, Fang XT, Toyonaga T, Lee S, Xu Y, Zheng MQ, Spurrier J, Huang Y, Strittmatter SM, Carson RE, Cai Z. Quantification of SV2A Binding in Rodent Brain Using [18F]SynVesT-1 and PET Imaging. Molecular Imaging And Biology 2020, 23: 372-381. PMID: 33258040, PMCID: PMC8105262, DOI: 10.1007/s11307-020-01567-9.Peer-Reviewed Original ResearchConceptsBrain stemAlzheimer's diseaseMin postinjectionAnimal modelsAPP/PS1 miceReference regionStandardized uptake value ratioDynamic PET imaging dataUptake value ratioRodent brain tissueStatic PET scansDifferent imaging windowsPET imaging dataWild-type controlsReference tissue modelPS1 miceAD pathogenesisTherapeutic effectMouse modelRodent modelsLittermate controlsPET scansRodent brainPreclinical imaging studiesTherapeutic drug efficacy
2019
Systematic and standardized comparison of reported amyloid-β receptors for sufficiency, affinity, and Alzheimer's disease relevance
Smith LM, Kostylev MA, Lee S, Strittmatter SM. Systematic and standardized comparison of reported amyloid-β receptors for sufficiency, affinity, and Alzheimer's disease relevance. Journal Of Biological Chemistry 2019, 294: 6042-6053. PMID: 30787106, PMCID: PMC6463724, DOI: 10.1074/jbc.ra118.006252.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseAD brainLeukocyte immunoglobulin-like receptorsNogo receptor 1Human AD brainsImmunoglobulin-like receptorsB member 2Brains of individualsReceptor candidatesSoluble AβOsDisease relevanceCell surface expressionHippocampal neuronsMouse modelSynthetic AβAβO bindingMemory impairmentReceptor 1Cellular prion proteinNeuronal synapsesNgR1Molecular pathologyAβAβ speciesMember 2
2017
Conditional Deletion of Prnp Rescues Behavioral and Synaptic Deficits after Disease Onset in Transgenic Alzheimer's Disease
Salazar SV, Gallardo C, Kaufman AC, Herber CS, Haas LT, Robinson S, Manson JC, Lee MK, Strittmatter SM. Conditional Deletion of Prnp Rescues Behavioral and Synaptic Deficits after Disease Onset in Transgenic Alzheimer's Disease. Journal Of Neuroscience 2017, 37: 9207-9221. PMID: 28842420, PMCID: PMC5607466, DOI: 10.1523/jneurosci.0722-17.2017.Peer-Reviewed Original ResearchConceptsDisease onsetAlzheimer's diseaseFamilial Alzheimer's diseaseDisease pathophysiologyCellular prion proteinHippocampal synapse lossSoluble oligomeric amyloidTransgenic Alzheimer's diseaseTime of diagnosisDisease-modifying therapiesAlzheimer's disease pathophysiologyPotential therapeutic targetAD-related phenotypesMonths of ageRole of PrPSymptom onsetSynaptic deficitsPrion proteinSynapse lossCatecholaminergic neuronsPlaque densityBehavioral deficitsOligomeric amyloidMouse modelPresent symptomsSilent Allosteric Modulation of mGluR5 Maintains Glutamate Signaling while Rescuing Alzheimer’s Mouse Phenotypes
Haas LT, Salazar SV, Smith LM, Zhao HR, Cox TO, Herber CS, Degnan AP, Balakrishnan A, Macor JE, Albright CF, Strittmatter SM. Silent Allosteric Modulation of mGluR5 Maintains Glutamate Signaling while Rescuing Alzheimer’s Mouse Phenotypes. Cell Reports 2017, 20: 76-88. PMID: 28683325, PMCID: PMC5547898, DOI: 10.1016/j.celrep.2017.06.023.Peer-Reviewed Original ResearchConceptsAD transgenic mouse modelDisease pathologyMetabotropic glutamate receptor 5Allosteric modulationGlutamate receptor 5Alzheimer's disease pathologyTransgenic mouse brainSilent allosteric modulatorsTransgenic mouse modelBroad therapeutic windowMouse phenotypeAD interventionSynaptic depletionBrain slicesGlutamate signalingMouse modelTherapeutic windowAD phenotypeReceptor 5Mouse brainAllosteric modulatorsMemory deficitsCellular prion proteinPathological roleMGluR5
2016
Cellular prion protein as a receptor for amyloid-β oligomers in Alzheimer's disease
Salazar SV, Strittmatter SM. Cellular prion protein as a receptor for amyloid-β oligomers in Alzheimer's disease. Biochemical And Biophysical Research Communications 2016, 483: 1143-1147. PMID: 27639648, PMCID: PMC5303667, DOI: 10.1016/j.bbrc.2016.09.062.Peer-Reviewed Original ResearchConceptsCellular prion proteinPrion proteinSignal transduction downstreamDisease pathophysiologyNeuronal surfaceMetabotropic glutamate receptor 5Neuronal cell surface moleculesGlutamate receptor 5Disease-associated stateAlzheimer's disease pathophysiologyAltered signal transductionTransduction downstreamSignal transductionGenetic evidenceSpecificity of bindingPyk2 kinaseCell surface moleculesFyn kinaseSynaptic dysfunctionAβO toxicitySynaptic transmissionMouse modelIntervention sitesReceptor 5Alzheimer's diseaseEarly Activation of Experience-Independent Dendritic Spine Turnover in a Mouse Model of Alzheimer's Disease.
Heiss JK, Barrett J, Yu Z, Haas LT, Kostylev MA, Strittmatter SM. Early Activation of Experience-Independent Dendritic Spine Turnover in a Mouse Model of Alzheimer's Disease. Cerebral Cortex 2016, 27: 3660-3674. PMID: 27365298, PMCID: PMC6059166, DOI: 10.1093/cercor/bhw188.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAlzheimer DiseaseAmyloid beta-Protein PrecursorAnalysis of VarianceAnimalsCerebral CortexDendritic SpinesDisease Models, AnimalGene Expression ProfilingGreen Fluorescent ProteinsHippocampusHumansImaging, Three-DimensionalImmunoprecipitationMiceMice, Inbred C57BLMice, TransgenicMutationNeuroimagingPlaque, AmyloidPresenilin-1Prion ProteinsProto-Oncogene Proteins c-fosSensory DeprivationTime FactorsVibrissaeConceptsAPP/PS1 miceDendritic spine turnoverSpine turnoverAlzheimer's diseasePS1 miceAged APP/PS1 miceYoung APP/PS1 miceAPP/PS1 mouse brainSoluble Aβ oligomersLipid-metabolizing genesAPPswe/Synaptic lossCerebral cortexSynapse densityAβ plaquesSynaptic dysregulationLack responsivenessMouse modelDendritic spinesPersistent spinesSynapse turnoverPlaque formationMouse brainYounger ageCellular prion protein
2015
Brivaracetam, but not ethosuximide, reverses memory impairments in an Alzheimer’s disease mouse model
Nygaard HB, Kaufman AC, Sekine-Konno T, Huh LL, Going H, Feldman SJ, Kostylev MA, Strittmatter SM. Brivaracetam, but not ethosuximide, reverses memory impairments in an Alzheimer’s disease mouse model. Alzheimer's Research & Therapy 2015, 7: 25. PMID: 25945128, PMCID: PMC4419386, DOI: 10.1186/s13195-015-0110-9.Peer-Reviewed Original ResearchAPP/PS1 miceSpike-wave dischargesAD mouse modelDisease mouse modelPS1 miceAmyloid precursor proteinMouse modelMemory impairmentDisease miceEpileptiform activitySurrogate markerTransgenic Alzheimer's disease miceAlzheimer's disease mouse modelSynaptic vesicle protein 2AAberrant network activityAlzheimer's disease miceReliable surrogate markerSpatial memory impairmentTransgenic mouse modelWidespread neuronal dysfunctionSpatial memory functionTransgenic mouse strainAntiepileptic drug ethosuximideIntroductionRecent studiesAD mice
2012
Role of Cellular Prion Protein in the Amyloid-β Oligomer Pathophysiology of Alzheimer’s Disease
Kaufman A, Strittmatter S. Role of Cellular Prion Protein in the Amyloid-β Oligomer Pathophysiology of Alzheimer’s Disease. 2012, 35-48. DOI: 10.1007/978-1-4614-5305-5_3.Peer-Reviewed Original ResearchAlzheimer's diseaseMouse modelCellular prion proteinPrimary histopathological featureAD mouse modelAmyloid-beta plaquesTransgenic mouse modelLong-term potentiationHistopathological featuresPrion proteinNeuronal dysfunctionNeurofibrillary tanglesMemory deficitsMemory lossDiseaseExact mechanismCommon formEssential mediatorPathophysiologyToxic effectsCell deathPrPCHigh-affinity binding partnerSynaptotoxicityDysfunction
2010
Nogo Receptor Deletion and Multimodal Exercise Improve Distinct Aspects of Recovery in Cervical Spinal Cord Injury
Harel NY, Song KH, Tang X, Strittmatter SM. Nogo Receptor Deletion and Multimodal Exercise Improve Distinct Aspects of Recovery in Cervical Spinal Cord Injury. Journal Of Neurotrauma 2010, 27: 2055-2066. PMID: 20809785, PMCID: PMC2978056, DOI: 10.1089/neu.2010.1491.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalExercise TherapyFemaleGene DeletionGenotypeGPI-Linked ProteinsHand StrengthImmunohistochemistryMaleMiceMice, Inbred C57BLMyelin ProteinsNeuronal PlasticityNogo Receptor 1Physical Conditioning, AnimalPostural BalanceReceptors, Cell SurfaceReproducibility of ResultsSerotoninSpinal CordSpinal Cord InjuriesWalkingConceptsSpinal cord injuryCord injuryCervical spinal cord injuryIncomplete spinal cord injuryCervical spinal injurySignificant histological differencesMultimodal exerciseExercise trainingLateral hemisectionReceptor deletionSpinal injuryLesion modelMouse modelAdult miceLesion sizeGene deletionHistological differencesNeural plasticityMild deficitsHistological analysisTraining regimenInjuryPhysical interventionsC3-C4MiceGenetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer’s disease mouse model
Zhang Y, Kurup P, Xu J, Carty N, Fernandez SM, Nygaard HB, Pittenger C, Greengard P, Strittmatter SM, Nairn AC, Lombroso PJ. Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer’s disease mouse model. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 19014-19019. PMID: 20956308, PMCID: PMC2973892, DOI: 10.1073/pnas.1013543107.Peer-Reviewed Original ResearchConceptsStriatal-enriched tyrosine phosphataseTyrosine phosphataseDisease mouse modelStriatal-enriched phosphataseAlzheimer's diseaseCellular deficitsGenetic manipulationNMDA receptorsMouse modelTriple transgenic AD mouse modelIncurable neurodegenerative disorderTransgenic AD mouse modelAlzheimer's disease mouse modelPathophysiology of ADSTEP inhibitorGenetic reductionAD mouse modelHuman AD patientsSoluble Aβ oligomersSynaptic functionPhosphataseNeurodegenerative disordersAD patientsDevastating disorderAnimal models
2009
Reticulon-4A (Nogo-A) Redistributes Protein Disulfide Isomerase to Protect Mice from SOD1-Dependent Amyotrophic Lateral Sclerosis
Yang YS, Harel NY, Strittmatter SM. Reticulon-4A (Nogo-A) Redistributes Protein Disulfide Isomerase to Protect Mice from SOD1-Dependent Amyotrophic Lateral Sclerosis. Journal Of Neuroscience 2009, 29: 13850-13859. PMID: 19889996, PMCID: PMC2797811, DOI: 10.1523/jneurosci.2312-09.2009.Peer-Reviewed Original ResearchMeSH KeywordsAlanineAmyotrophic Lateral SclerosisAnimalsChlorocebus aethiopsCOS CellsGlycineMaleMiceMice, CongenicMice, Inbred C57BLMice, KnockoutMice, TransgenicMolecular ChaperonesMyelin ProteinsNeuroprotective AgentsNogo ProteinsProtein Disulfide-IsomerasesSuperoxide DismutaseSuperoxide Dismutase-1Tissue DistributionConceptsAmyotrophic lateral sclerosisLateral sclerosisFatal motor neuron diseaseSubset of patientsALS disease progressionMotor neuron diseaseTransgenic mouse modelPotential therapeutic approachEndoplasmic reticulum stressHomogeneous expression patternNeuron diseaseALS pathophysiologyDisease onsetDisease progressionTherapeutic approachesMouse modelChaperone protein disulfide isomeraseReticulum stressNovel intracellular roleReticulon proteinsMiceSclerosisPatientsUnfolded protein responseNogoA