2022
Metabolism Connects Body, Brain, and Behavior
Horvath TL. Metabolism Connects Body, Brain, and Behavior. Biological Psychiatry 2022, 91: 854-855. PMID: 35501105, DOI: 10.1016/j.biopsych.2022.03.015.Peer-Reviewed Original ResearchBrain
2021
Therapy for Alzheimer’s disease: Missing targets and functional markers?
Stoiljkovic M, Horvath TL, Hajós M. Therapy for Alzheimer’s disease: Missing targets and functional markers? Ageing Research Reviews 2021, 68: 101318. PMID: 33711510, PMCID: PMC8131215, DOI: 10.1016/j.arr.2021.101318.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseNew symptomatic treatmentsNeural network integrityClinical characteristicsNext-generation therapiesSymptomatic treatmentOutcome biomarkerTau pathologyFluid biomarkersPlasma biomarkersDisease progressionEffective therapyNeurophysiological biomarkersTreatment candidatesCerebrospinal fluidNovel biomarkersTranslational studiesTreatment interventionsDiseaseTarget engagementTherapyBiomarkersCurrent conceptsMultiple biomarkersDrug targets
2018
Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism
García-Cáceres C, Balland E, Prevot V, Luquet S, Woods SC, Koch M, Horvath TL, Yi CX, Chowen JA, Verkhratsky A, Araque A, Bechmann I, Tschöp MH. Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism. Nature Neuroscience 2018, 22: 7-14. PMID: 30531847, DOI: 10.1038/s41593-018-0286-y.Peer-Reviewed Original ResearchConceptsControl of metabolismNon-neuronal cellsNeuronal-glial networksFunctional interactionSpecific neuronal subpopulationsEnergy metabolismHypothalamic feeding circuitsRole of astrocytesPhysiological responsesGlial-neuronal interactionsMetabolismFood-related cuesNeuronal subpopulationsSystemic metabolismFood intakeBrain controlMetabolic statusRecent advancesMicrogliaAstrocytesGeneticsTanycytesComplex setBiologyInteroceptive signalsThe 7q11.23 Protein DNAJC30 Interacts with ATP Synthase and Links Mitochondria to Brain Development
Tebbenkamp ATN, Varela L, Choi J, Paredes MI, Giani AM, Song JE, Sestan-Pesa M, Franjic D, Sousa AMM, Liu ZW, Li M, Bichsel C, Koch M, Szigeti-Buck K, Liu F, Li Z, Kawasawa YI, Paspalas CD, Mineur YS, Prontera P, Merla G, Picciotto MR, Arnsten AFT, Horvath TL, Sestan N. The 7q11.23 Protein DNAJC30 Interacts with ATP Synthase and Links Mitochondria to Brain Development. Cell 2018, 175: 1088-1104.e23. PMID: 30318146, PMCID: PMC6459420, DOI: 10.1016/j.cell.2018.09.014.Peer-Reviewed Original ResearchConceptsCopy number variationsATP synthase dimersOxidative phosphorylation supercomplexesHuman neurodevelopmental disordersATP synthaseWS pathogenesisGene contributionMitochondrial featuresBrain developmentWilliams syndromeMitochondrial dysfunctionNeocortical pyramidal neuronsNeural phenotypesMitochondriaPyramidal neuronsMachineryMorphological featuresNeurodevelopmental disordersDysfunctionSupercomplexesPhenotypeNeurophysiological 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 ResearchConceptsTgF344-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 drugs
2016
Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia
Onorati M, Li Z, Liu F, Sousa AMM, Nakagawa N, Li M, Dell’Anno M, Gulden FO, Pochareddy S, Tebbenkamp AT, Han W, Pletikos M, Gao T, Zhu Y, Bichsel C, Varela L, Szigeti-Buck K, Lisgo S, Zhang Y, Testen A, Gao XB, Mlakar J, Popovic M, Flamand M, Strittmatter SM, Kaczmarek LK, Anton ES, Horvath TL, Lindenbach BD, Sestan N. Zika Virus Disrupts Phospho-TBK1 Localization and Mitosis in Human Neuroepithelial Stem Cells and Radial Glia. Cell Reports 2016, 16: 2576-2592. PMID: 27568284, PMCID: PMC5135012, DOI: 10.1016/j.celrep.2016.08.038.Peer-Reviewed Original ResearchMeSH KeywordsAxl Receptor Tyrosine KinaseBrainCell DeathCentrosomeFetusGene Expression ProfilingHumansImmunity, InnateMicrocephalyMitochondriaMitosisNeocortexNeural Stem CellsNeuroepithelial CellsNeurogliaNeuronsNeuroprotective AgentsNucleosidesPhosphorylationProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesSpinal CordTranscription, GeneticVirus ReplicationZika VirusZika Virus InfectionConceptsRadial glial cellsNES cellsNeuroepithelial stem cellsZIKV infectionFetal brain slicesStem cellsEarly human neurodevelopmentHuman neuroepithelial stem cellsHuman neural stem cellsCell deathSingle-cell RNA-seqNeural stem cellsNeurodevelopment defectsZIKV replicationGlial cellsBrain slicesPotential treatmentRadial gliaZika virusPhospho-TBK1Neurodevelopmental defectsRNA-seqSupernumerary centrosomesNucleoside analoguesHuman neurodevelopmentVaginal 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 consequences
2015
Neuronal Regulation of Energy Homeostasis: Beyond the Hypothalamus and Feeding
Waterson MJ, Horvath TL. Neuronal Regulation of Energy Homeostasis: Beyond the Hypothalamus and Feeding. Cell Metabolism 2015, 22: 962-970. PMID: 26603190, DOI: 10.1016/j.cmet.2015.09.026.Peer-Reviewed Original Research
2013
Maternal and Offspring Pools of Osteocalcin Influence Brain Development and Functions
Oury F, Khrimian L, Denny CA, Gardin A, Chamouni A, Goeden N, Huang YY, Lee H, Srinivas P, Gao XB, Suyama S, Langer T, Mann JJ, Horvath TL, Bonnin A, Karsenty G. Maternal and Offspring Pools of Osteocalcin Influence Brain Development and Functions. Cell 2013, 155: 228-241. PMID: 24074871, PMCID: PMC3864001, DOI: 10.1016/j.cell.2013.08.042.Peer-Reviewed Original ResearchConceptsOsteoblast-derived hormone osteocalcinBrain developmentBone-derived signalsBlood-brain barrierFetal brain developmentInfluences brain developmentBone massNeuronal apoptosisMonoamine neurotransmittersGABA synthesisMemory deficitsNeuroanatomical defectsOffspring poolPostnatal functionMaternal genotypeMetabolic functionsOsteocalcinPowerful regulationBrainMaternal influenceRegulationBrainstemPregnancyHippocampusMidbrainNatural birth-induced UCP2 in brain development
Seli E, Horvath TL. Natural birth-induced UCP2 in brain development. Reviews In Endocrine And Metabolic Disorders 2013, 14: 347-350. PMID: 23979530, DOI: 10.1007/s11154-013-9262-8.Peer-Reviewed Original ResearchConceptsVaginal birthPost-operative surgical careLong-term outcomesEarly postnatal periodWild-type littermatesAdult brain structureUCP2 mRNA expressionTerm outcomesSurgical techniqueSurgical carePostnatal periodSurgical meansHippocampal formationMore deliveriesSynapse formationAxonal outgrowthC-sectionKnockout animalsMRNA expressionUCP2 expressionBrain developmentBrain structuresNeuronal differentiationBirthHippocampusAntibodies to cannabinoid type 1 receptor co‐react with stomatin‐like protein 2 in mouse brain mitochondria
Morozov YM, Dominguez MH, Varela L, Shanabrough M, Koch M, Horvath TL, Rakic P. Antibodies to cannabinoid type 1 receptor co‐react with stomatin‐like protein 2 in mouse brain mitochondria. European Journal Of Neuroscience 2013, 38: 2341-2348. PMID: 23617247, PMCID: PMC3902808, DOI: 10.1111/ejn.12237.Peer-Reviewed Original ResearchConceptsStomatin-like protein 2Type 1 receptorPresence of CB1Protein 2Anti-CB1 antibodySynthetic cannabinoid WINMouse brain mitochondriaCerebral cortexEndocannabinoid signalingBrain cellsCannabinoid WINNeuronal mitochondriaBrain mitochondriaAntibodiesMitochondrial functionCB1Polyclonal antibodiesCortexMitochondrial preparationsSerumReceptors
2012
Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis
Varela L, Horvath TL. Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis. EMBO Reports 2012, 13: 1079-1086. PMID: 23146889, PMCID: PMC3512417, DOI: 10.1038/embor.2012.174.Peer-Reviewed Original ResearchConceptsGlucose homeostasisEnergy homeostasisPrevalence of obesityWhole-body energy homeostasisBody energy homeostasisAnorectic hormonesAgRP neuronsObese patientsProtein (AgRP) neuronsCentral effectsHypothalamic proopiomelanocortinBody weightInsulin actionLeptinHormonal actionMajor targetInsulin pathwayHomeostasisInsulinNeuronsHormoneBrainLatest findingsEnergy balanceSteady rise
2011
CPG15 regulates synapse stability in the developing and adult brain
Fujino T, Leslie JH, Eavri R, Chen JL, Lin WC, Flanders GH, Borok E, Horvath TL, Nedivi E. CPG15 regulates synapse stability in the developing and adult brain. Genes & Development 2011, 25: 2674-2685. PMID: 22190461, PMCID: PMC3248687, DOI: 10.1101/gad.176172.111.Peer-Reviewed Original ResearchConceptsSynaptic maturationDendritic spinesFunctional synaptic contactsNeural circuit developmentSynaptic contactsSpine maintenanceDiolistic labelingDendritic arborsMature brainCircuit refinementSynapse stabilityAdult brainKnockout miceSynapse stabilizationCPG15Active synapsesSpine numberActivity-dependent synapseDevelopmental maturationSpineNeuronal branchesCircuit developmentGradual attritionBrainSynapsesCortical Glial Fibrillary Acidic Protein-Positive Cells Generate Neurons after Perinatal Hypoxic Injury
Bi B, Salmaso N, Komitova M, Simonini MV, Silbereis J, Cheng E, Kim J, Luft S, Ment LR, Horvath TL, Schwartz ML, Vaccarino FM. Cortical Glial Fibrillary Acidic Protein-Positive Cells Generate Neurons after Perinatal Hypoxic Injury. Journal Of Neuroscience 2011, 31: 9205-9221. PMID: 21697371, PMCID: PMC3142780, DOI: 10.1523/jneurosci.0518-11.2011.Peer-Reviewed Original ResearchConceptsGlial fibrillary acidic protein-positive cellsCortical excitatory neuronsProtein-positive cellsPerinatal hypoxic injuryPostnatal hypoxiaGenetic fate mappingCortical astrogliaPremature childrenHypoxic injuryBrain injuryNew neuronsPreterm childrenNeurogenic nicheCognitive recoveryExcitatory neuronsGenerate neuronsNeuronal fateNeuronsHypoxiaCortical parenchymaInjuryParenchymaFate mappingCellsChildrenEffects of chronic weight perturbation on energy homeostasis and brain structure in mice
Ravussin Y, Gutman R, Diano S, Shanabrough M, Borok E, Sarman B, Lehmann A, LeDuc CA, Rosenbaum M, Horvath TL, Leibel RL. Effects of chronic weight perturbation on energy homeostasis and brain structure in mice. AJP Regulatory Integrative And Comparative Physiology 2011, 300: r1352-r1362. PMID: 21411766, PMCID: PMC3119157, DOI: 10.1152/ajpregu.00429.2010.Peer-Reviewed Original ResearchConceptsDiet-induced obeseEnergy expenditureArcuate nucleus proopiomelanocortin neuronsWeight lossWeight-reduced individualsSustained weight lossReduced body weightObese human subjectsCentral nervous systemHuman subjectsSustained weight gainProopiomelanocortin neuronsBody massUpward resettingMale miceExcitatory synapsesBody fatMouse modelBody weightNervous systemSynaptic changesPersistent decreaseEnergy homeostasisWeight gainBrain structures
2009
Feeding signals and brain circuitry
Dietrich MO, Horvath TL. Feeding signals and brain circuitry. European Journal Of Neuroscience 2009, 30: 1688-1696. PMID: 19878280, DOI: 10.1111/j.1460-9568.2009.06963.x.Peer-Reviewed Original Research
2008
Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia
Xie X, Wisor JP, Hara J, Crowder TL, LeWinter R, Khroyan TV, Yamanaka A, Diano S, Horvath TL, Sakurai T, Toll L, Kilduff TS. Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia. Journal Of Clinical Investigation 2008, 118: 2471-2481. PMID: 18551194, PMCID: PMC2423866, DOI: 10.1172/jci35115.Peer-Reviewed Original ResearchMeSH KeywordsAnalgesiaAnimalsAtaxin-3Behavior, AnimalBrainCalciumCytoplasmElectrophysiologyFemaleHypothalamus, PosteriorImmunohistochemistryIntracellular Signaling Peptides and ProteinsMaleMembrane PotentialsMiceMice, Inbred C57BLMice, TransgenicNarcotic AntagonistsNeuronsNeuropeptidesNociceptin ReceptorNuclear ProteinsOpioid PeptidesOrexinsPain ThresholdPresynaptic TerminalsReaction TimeReceptors, OpioidStress, PhysiologicalTetrodotoxinTranscription FactorsConceptsStress-induced analgesiaHcrt neuronsWild-type miceHypocretin/orexinNociceptin/orphanin FQMouse hypothalamic slicesCorticotropin-releasing factorPatch-clamp recordingsOrexin/ataxinPostsynaptic effectsPresynaptic releaseOrphanin FQElectron microscopic levelHypothalamic slicesSynaptic contactsHcrt-1Hcrt systemMouse modelAnalgesiaClamp recordingsPeptidergic systemsAction potentialsBrain tissueNeuronsInput resistanceBrain circuits regulating energy homeostasis
Abizaid A, Horvath TL. Brain circuits regulating energy homeostasis. Peptides 2008, 149: 3-10. PMID: 18514925, PMCID: PMC2605273, DOI: 10.1016/j.regpep.2007.10.006.Peer-Reviewed Original Research
2006
Thoughts for Food: Brain Mechanisms and Peripheral Energy Balance
Abizaid A, Gao Q, Horvath TL. Thoughts for Food: Brain Mechanisms and Peripheral Energy Balance. Neuron 2006, 51: 691-702. PMID: 16982416, DOI: 10.1016/j.neuron.2006.08.025.Peer-Reviewed Original Research