2022
TREM2 Deficiency Disrupts Network Oscillations Leading to Epileptic Activity and Aggravates Amyloid-β-Related Hippocampal Pathophysiology in Mice
Stoiljkovic M, Gutierrez KO, Kelley C, Horvath TL, Hajós M. TREM2 Deficiency Disrupts Network Oscillations Leading to Epileptic Activity and Aggravates Amyloid-β-Related Hippocampal Pathophysiology in Mice. Journal Of Alzheimer's Disease 2022, 88: 837-847. PMID: 34120899, PMCID: PMC8898080, DOI: 10.3233/jad-210041.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAnimalsDisease Models, AnimalEpilepsyHippocampusMembrane GlycoproteinsMiceMice, TransgenicMicrogliaReceptors, ImmunologicConceptsAlzheimer's diseaseMicroglial functionTREM2 functionTheta-phase gamma-amplitude couplingHippocampal network functionSpontaneous epileptiform seizuresNetwork oscillationsTransgenic AD modelHippocampal neuronal excitabilityMyeloid cells 2Clinical Alzheimer's diseaseWild-type miceHippocampal network oscillationsHippocampal pathophysiologyProgressive dementiaTau pathologyUrethane anesthesiaAD pathophysiologyNeuronal excitabilityEpileptiform seizuresEpileptic activityAD modelTREM2Disease pathologyCells 2
2021
Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice
Ryu S, Shchukina I, Youm YH, Qing H, Hilliard B, Dlugos T, Zhang X, Yasumoto Y, Booth CJ, Fernández-Hernando C, Suárez Y, Khanna K, Horvath TL, Dietrich MO, Artyomov M, Wang A, Dixit VD. Ketogenic diet restrains aging-induced exacerbation of coronavirus infection in mice. ELife 2021, 10: e66522. PMID: 34151773, PMCID: PMC8245129, DOI: 10.7554/elife.66522.Peer-Reviewed Original ResearchConceptsΓδ T cellsKetogenic dietCoronavirus infectionAged miceT cellsHigher systemic inflammationInfected aged miceCOVID-19 severityCOVID-19 infectionActivation of ketogenesisMouse hepatitis virus strain A59Systemic inflammationInflammatory damageInfluenza infectionClinical hallmarkNLRP3 inflammasomeImmune surveillanceAdipose tissuePotential treatmentInfectionMiceStrongest predictorLungMortalityAgeAge‐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 cortexNeuroinvasion of SARS-CoV-2 in human and mouse brain
Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, Lu P, Weizman OE, Liu F, Dai Y, Szigeti-Buck K, Yasumoto Y, Wang G, Castaldi C, Heltke J, Ng E, Wheeler J, Alfajaro MM, Levavasseur E, Fontes B, Ravindra NG, Van Dijk D, Mane S, Gunel M, Ring A, Kazmi SAJ, Zhang K, Wilen CB, Horvath TL, Plu I, Haik S, Thomas JL, Louvi A, Farhadian SF, Huttner A, Seilhean D, Renier N, Bilguvar K, Iwasaki A. Neuroinvasion of SARS-CoV-2 in human and mouse brain. Journal Of Experimental Medicine 2021, 218: e20202135. PMID: 33433624, PMCID: PMC7808299, DOI: 10.1084/jem.20202135.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin-Converting Enzyme 2AnimalsAntibodies, BlockingCerebral CortexCOVID-19Disease Models, AnimalFemaleHumansMaleMiceMiddle AgedNeuronsOrganoidsSARS-CoV-2ConceptsSARS-CoV-2Central nervous systemSARS-CoV-2 neuroinvasionImmune cell infiltratesCOVID-19 patientsType I interferon responseMultiple organ systemsCOVID-19I interferon responseHuman brain organoidsNeuroinvasive capacityCNS infectionsCell infiltrateNeuronal infectionPathological featuresCortical neuronsRespiratory diseaseDirect infectionCerebrospinal fluidNervous systemMouse brainInterferon responseOrgan systemsHuman ACE2Infection
2018
Neurophysiological signals as predictive translational biomarkers for Alzheimer’s disease treatment: effects of donepezil on neuronal network oscillations in TgF344-AD rats
Stoiljkovic M, Kelley C, Horvath TL, Hajós M. Neurophysiological signals as predictive translational biomarkers for Alzheimer’s disease treatment: effects of donepezil on neuronal network oscillations in TgF344-AD rats. Alzheimer's Research & Therapy 2018, 10: 105. PMID: 30301466, PMCID: PMC6178257, DOI: 10.1186/s13195-018-0433-4.Peer-Reviewed Original ResearchConceptsTgF344-AD ratsWild-type ratsEffects of donepezilOscillatory abnormalitiesTgF344-ADStimulation-induced hippocampal theta oscillationAdult wild-type ratsDisease pathologyAccumulation of amyloidHigh-voltage spindle activityDisease-modifying potentialSeizure-like activityAlzheimer's disease pathologySpontaneous cortical activityAge-dependent reductionDisease treatmentHigh-voltage spindlesAcetylcholine esterase inhibitorsNeuronal network oscillationsAlzheimer's disease treatmentHippocampal theta oscillationsDonepezil treatmentCholinergic toneUrethane anesthesiaClinical effectivenessAltered Cortical and Hippocampal Excitability in TgF344-AD Rats Modeling Alzheimer’s Disease Pathology
Stoiljkovic M, Kelley C, Stutz B, Horvath TL, Hajós M. Altered Cortical and Hippocampal Excitability in TgF344-AD Rats Modeling Alzheimer’s Disease Pathology. Cerebral Cortex 2018, 29: 2716-2727. PMID: 29920597, PMCID: PMC7302691, DOI: 10.1093/cercor/bhy140.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAnimalsBrainDisease Models, AnimalEvoked Potentials, AuditoryFemaleMaleRatsRats, Inbred F344Rats, TransgenicConceptsTgF344-AD ratsHippocampal theta oscillationsAlzheimer's diseaseDisease pathologyTheta-phase gamma-amplitude couplingAge-matched wild-type counterpartsAD pathological featuresDisease-modifying therapiesAccumulation of amyloidPredictive animal modelsAlzheimer's disease pathologyHigh-voltage spindlesTheta oscillationsSignificant age-dependent declineAge-dependent declineHippocampal excitabilitySharp-wave ripplesAβ accumulationNeuronal lossAD ratsPathological featuresUrethane anesthesiaAD patientsAuditory gatingAD drugsType I interferons instigate fetal demise after Zika virus infection
Yockey LJ, Jurado KA, Arora N, Millet A, Rakib T, Milano KM, Hastings AK, Fikrig E, Kong Y, Horvath TL, Weatherbee S, Kliman HJ, Coyne CB, Iwasaki A. Type I interferons instigate fetal demise after Zika virus infection. Science Immunology 2018, 3 PMID: 29305462, PMCID: PMC6049088, DOI: 10.1126/sciimmunol.aao1680.Peer-Reviewed Original ResearchConceptsZika virus infectionZIKV infectionI IFNsI interferonType I interferonGrowth restrictionFetal demiseVirus infectionSevere fetal growth restrictionType I IFNsChorionic villous explantsAdverse fetal outcomesCongenital viral infectionFetal growth restrictionMaternal-fetal barrierType IFunctional type IPlacental damageFetal outcomesPregnancy complicationsEarly pregnancyFetal resorptionZIKV diseasePregnant damsSpontaneous abortion
2017
Fetal Growth Restriction Caused by Sexual Transmission of Zika Virus in Mice
Uraki R, Jurado KA, Hwang J, Szigeti-Buck K, Horvath TL, Iwasaki A, Fikrig E. Fetal Growth Restriction Caused by Sexual Transmission of Zika Virus in Mice. The Journal Of Infectious Diseases 2017, 215: 1720-1724. PMID: 28472297, PMCID: PMC5853330, DOI: 10.1093/infdis/jix204.Peer-Reviewed Original ResearchConceptsZika virusSexual transmissionWeight of fetusesFetal growth restrictionNaive female miceType I interferon receptorEmbryonic day 18.5Female miceGrowth restrictionMale miceOcular deformityMosquito bitesControl groupDay 18.5Fetal abnormalitiesSexual contactInterferon receptorMiceFetusesInfected malesVirusDeformityAbnormalitiesReceptors
2016
Vaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection
Yockey LJ, Varela L, Rakib T, Khoury-Hanold W, Fink SL, Stutz B, Szigeti-Buck K, Van den Pol A, Lindenbach BD, Horvath TL, Iwasaki A. Vaginal Exposure to Zika Virus during Pregnancy Leads to Fetal Brain Infection. Cell 2016, 166: 1247-1256.e4. PMID: 27565347, PMCID: PMC5006689, DOI: 10.1016/j.cell.2016.08.004.Peer-Reviewed Original ResearchMeSH KeywordsAbortion, HabitualAnimalsBrainBrain DiseasesDisease Models, AnimalFemaleFetal Growth RetardationInterferon Regulatory Factor-3MiceMice, Inbred C57BLMice, Mutant StrainsPregnancyPregnancy Complications, InfectiousReceptor, Interferon alpha-betaVaginaVirus ReplicationZika VirusZika Virus InfectionConceptsZika virusFetal brain infectionFetal growth restrictionLocal viral replicationWild-type miceType I interferon receptorZIKV challengeTranscription factor IRF3Vaginal exposureGenital mucosaBrain infectionWT miceEarly pregnancyZIKV infectionGrowth restrictionPregnant damsVaginal infectionsZIKV replicationFetal brainMouse modelIFN pathwayVaginal tractUnborn fetusViral replicationDisease consequencesViral Spread to Enteric Neurons Links Genital HSV-1 Infection to Toxic Megacolon and Lethality
Khoury-Hanold W, Yordy B, Kong P, Kong Y, Ge W, Szigeti-Buck K, Ralevski A, Horvath TL, Iwasaki A. Viral Spread to Enteric Neurons Links Genital HSV-1 Infection to Toxic Megacolon and Lethality. Cell Host & Microbe 2016, 19: 788-799. PMID: 27281569, PMCID: PMC4902295, DOI: 10.1016/j.chom.2016.05.008.Peer-Reviewed Original ResearchConceptsGenital HSV-1 infectionEnteric nervous systemHSV-1 infectionSensory nervous systemNervous systemGenital herpesToxic megacolonHSV-1Genital mucosal epithelial cellsPeripheral sensory nervous systemDorsal root gangliaPathological inflammatory responsesMucosal epithelial cellsHerpes simplex virus 1Simplex virus 1Urinary retentionEnteric neuronsLaxative treatmentAutonomic gangliaRoot gangliaInflammatory responseViral gene transcriptionMouse modelInfectionEpithelial cells
2015
The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease
Youm YH, Nguyen KY, Grant RW, Goldberg EL, Bodogai M, Kim D, D'Agostino D, Planavsky N, Lupfer C, Kanneganti TD, Kang S, Horvath TL, Fahmy TM, Crawford PA, Biragyn A, Alnemri E, Dixit VD. The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease. Nature Medicine 2015, 21: 263-269. PMID: 25686106, PMCID: PMC4352123, DOI: 10.1038/nm.3804.Peer-Reviewed Original Research
2013
Intranasal epidermal growth factor treatment rescues neonatal brain injury
Scafidi J, Hammond TR, Scafidi S, Ritter J, Jablonska B, Roncal M, Szigeti-Buck K, Coman D, Huang Y, McCarter RJ, Hyder F, Horvath TL, Gallo V. Intranasal epidermal growth factor treatment rescues neonatal brain injury. Nature 2013, 506: 230-234. PMID: 24390343, PMCID: PMC4106485, DOI: 10.1038/nature12880.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntranasalAnimalsAnimals, NewbornBrain InjuriesCell DifferentiationCell DivisionCell LineageCell SurvivalDemyelinating DiseasesDisease Models, AnimalEpidermal Growth FactorErbB ReceptorsHumansHypoxiaInfant, Premature, DiseasesMaleMiceMolecular Targeted TherapyOligodendrogliaRegenerationSignal TransductionStem CellsTime FactorsConceptsDiffuse white matter injuryNeonatal brain injuryVery preterm infantsWhite matter injuryOligodendrocyte precursor cellsEpidermal growth factor receptorGrowth factor treatmentGrowth factor receptorPreterm infantsFunctional recoveryBrain injurySuch injuriesEpidermal growth factor treatmentMouse modelFactor treatmentInjuryFactor receptorPrecursor cellsInfantsReceptors
2005
Uncoupling Protein-2 Is Critical for Nigral Dopamine Cell Survival in a Mouse Model of Parkinson's Disease
Andrews ZB, Horvath B, Barnstable CJ, Elseworth J, Yang L, Beal MF, Roth RH, Matthews RT, Horvath TL. Uncoupling Protein-2 Is Critical for Nigral Dopamine Cell Survival in a Mouse Model of Parkinson's Disease. Journal Of Neuroscience 2005, 25: 184-191. PMID: 15634780, PMCID: PMC6725213, DOI: 10.1523/jneurosci.4269-04.2005.Peer-Reviewed Original ResearchMeSH Keywords1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine1-Methyl-4-phenylpyridiniumAnimalsCell SurvivalCorpus StriatumDisease Models, AnimalDopamineHumansImmunohistochemistryIon ChannelsMaleMembrane Transport ProteinsMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMitochondriaMitochondrial ProteinsOxygen ConsumptionParkinsonian DisordersReactive Oxygen SpeciesSubstantia NigraUncoupling Protein 2ConceptsProtein 2Mitochondrial ROS productionLack of UCP2Reactive oxygen species productionGenetic manipulationOxygen species productionMitochondria numberCell metabolismATP synthesisCell survivalOverexpression of UCP2Wild-type controlsMitochondrial uncouplingNovel therapeutic targetROS productionUCP2Species productionElectron microscopic analysisOverexpressionCell functionUCP2 overexpressionDopamine cell survivalTherapeutic targetFluorescent ethidiumDopamine cell function
2003
Coenzyme Q Induces Nigral Mitochondrial Uncoupling and Prevents Dopamine Cell Loss in a Primate Model of Parkinson’s Disease
Horvath TL, Diano S, Leranth C, Garcia-Segura LM, Cowley MA, Shanabrough M, Elsworth JD, Sotonyi P, Roth RH, Dietrich EH, Matthews RT, Barnstable CJ, Redmond DE. Coenzyme Q Induces Nigral Mitochondrial Uncoupling and Prevents Dopamine Cell Loss in a Primate Model of Parkinson’s Disease. Endocrinology 2003, 144: 2757-2760. PMID: 12810526, DOI: 10.1210/en.2003-0163.Peer-Reviewed Original ResearchConceptsDopamine cell lossParkinson's diseaseCell lossShort-term oral administrationMitochondrial uncouplingSubstantia nigraDopamine neuronsTetrahydropyridine (MPTP) administrationCoenzyme QPrimate modelOral administrationDiseaseOxidative stressState 4 respirationMitochondrial uncoupling proteinAdministrationUncoupling proteinUncouplingNeuronsNigraTetrahydropyridine
2002
Brain mitochondrial uncoupling protein 2 (UCP2): a protective stress signal in neuronal injury
Bechmann I, Diano S, Warden CH, Bartfai T, Nitsch R, Horvath TL. Brain mitochondrial uncoupling protein 2 (UCP2): a protective stress signal in neuronal injury. Biochemical Pharmacology 2002, 64: 363-367. PMID: 12147286, DOI: 10.1016/s0006-2952(02)01166-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, Genetically ModifiedBrain InjuriesDisease Models, AnimalEntorhinal CortexGene Transfer TechniquesImmunohistochemistryIon ChannelsLearningMaleMembrane Transport ProteinsMemoryMiceMice, Inbred C57BLMitochondriaMitochondrial ProteinsNerve DegenerationNeuronsProtective AgentsProteinsRatsRats, WistarSignal TransductionStress, PhysiologicalUncoupling Protein 2