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 ResearchConceptsAlzheimer'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
Ucp2-dependent microglia-neuronal coupling controls ventral hippocampal circuit function and anxiety-like behavior
Yasumoto Y, Stoiljkovic M, Kim JD, Sestan-Pesa M, Gao XB, Diano S, Horvath TL. Ucp2-dependent microglia-neuronal coupling controls ventral hippocampal circuit function and anxiety-like behavior. Molecular Psychiatry 2021, 26: 2740-2752. PMID: 33879866, PMCID: PMC8056795, DOI: 10.1038/s41380-021-01105-1.Peer-Reviewed Original ResearchConceptsAnxiety-like behaviorReactive oxygen speciesMicroglia-synapse contactsSpine synapse numberHippocampal circuit functionNeuronal circuit dysfunctionMicroglial productionVentral hippocampusCircuit dysfunctionSpine synapsesSynapse numberAdult brainTransient riseMitochondrial ROS generationMicrogliaBrain functionConditional ablationPhagocytic inclusionsSynaptic elementsProtein 2ROS generationSignificant reductionCircuit functionConsequent accumulationOxygen species
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 effectivenessMyeloid sirtuin1 deficiency aggravates hippocampal inflammation in mice fed high-fat diets
Kim KE, Jeong EA, Lee JY, Yi CO, Park KA, Jin Z, Lee JE, Horvath TL, Roh GS. Myeloid sirtuin1 deficiency aggravates hippocampal inflammation in mice fed high-fat diets. Biochemical And Biophysical Research Communications 2018, 499: 1025-1031. PMID: 29634925, DOI: 10.1016/j.bbrc.2018.04.044.Peer-Reviewed Original ResearchConceptsSirt1 KO miceHigh-fat dietInsulin resistanceKO miceLipocalin-2Inflammation-induced insulin resistanceObesity-associated insulin resistanceAnti-inflammatory effectsPrecursor protein levelsWild-type miceHippocampal inflammationWT miceMacrophage infiltrationObese miceLCN2 expressionSIRT1 knockoutType miceHFDAdipose tissueMiceProtein levelsNeuroinflammationSIRT1DietDeficiency
2016
Mitochondria controlled by UCP2 determine hypoxia-induced synaptic remodeling in the cortex and hippocampus
Varela L, Schwartz ML, Horvath TL. Mitochondria controlled by UCP2 determine hypoxia-induced synaptic remodeling in the cortex and hippocampus. Neurobiology Of Disease 2016, 90: 68-74. PMID: 26777666, DOI: 10.1016/j.nbd.2016.01.004.Peer-Reviewed Original ResearchConceptsHippocampal neuronsMitochondria-endoplasmic reticulum interactionUCP2-KO miceEarly postnatal exposureLoss of synapsesOxygen tensionHigher brain regionsAdaptive mitochondrial responsesProtein 2 expressionHypothalamic circuitsPostnatal exposureKO miceSynaptic remodelingSystemic metabolismSynaptic inputsBrain cellsMetabolic controlNeuronal mitochondriaBrain regionsAdaptive responseNeuronsHippocampusMitochondrial dynamicsMetabolic challengesCortex
2015
Calcineurin Aγ is a Functional Phosphatase That Modulates Synaptic Vesicle Endocytosis*
Cottrell JR, Li B, Kyung JW, Ashford CJ, Mann JJ, Horvath TL, Ryan TA, Kim SH, Gerber DJ. Calcineurin Aγ is a Functional Phosphatase That Modulates Synaptic Vesicle Endocytosis*. Journal Of Biological Chemistry 2015, 291: 1948-1956. PMID: 26627835, PMCID: PMC4722470, DOI: 10.1074/jbc.m115.705319.Peer-Reviewed Original ResearchConceptsSynaptic vesicle cyclingVesicle cyclingHippocampal neuronsPsychiatric diseasesSynaptic vesicle endocytosisCultured rat hippocampal neuronsRNAi-mediated knockdownCalcineurin catalytic subunitRat hippocampal neuronsFunctional phosphataseCombination of immunocytochemistryVesicle endocytosisLow expression levelsCatalytic subunitPresynaptic substratePresynaptic terminalsPresynaptic functionΓ isoformsCalcineurin AαCatalytic isoformsImmuno-EMSpecific functionsExpression levelsMost tissuesPPP3CC
2012
Ucp2 Induced by Natural Birth Regulates Neuronal Differentiation of the Hippocampus and Related Adult Behavior
Simon-Areces J, Dietrich MO, Hermes G, Garcia-Segura LM, Arevalo MA, Horvath TL. Ucp2 Induced by Natural Birth Regulates Neuronal Differentiation of the Hippocampus and Related Adult Behavior. PLOS ONE 2012, 7: e42911. PMID: 22905184, PMCID: PMC3414493, DOI: 10.1371/journal.pone.0042911.Peer-Reviewed Original ResearchConceptsUCP2 expressionCellular stressHippocampal neuronsChemical inhibitionMitochondrial bioenergeticsNeuronal differentiationGenetic ablationNatural birthProtein 2Adult behaviorCell proliferationCritical roleAdult brainNeuronal numberExpressionBioenergeticsNeuronsBirthDifferentiationRegulationProliferationSynaptogenesisVitroNeuroprotectionHippocampus
2008
Exercise-Induced Synaptogenesis in the Hippocampus Is Dependent on UCP2-Regulated Mitochondrial Adaptation
Dietrich MO, Andrews ZB, Horvath TL. Exercise-Induced Synaptogenesis in the Hippocampus Is Dependent on UCP2-Regulated Mitochondrial Adaptation. Journal Of Neuroscience 2008, 28: 10766-10771. PMID: 18923051, PMCID: PMC3865437, DOI: 10.1523/jneurosci.2744-08.2008.Peer-Reviewed Original ResearchConceptsSynaptic plasticityVoluntary exerciseEssential organellesUCP2 functionProtein-2 mRNA expressionDendritic spine synapsesBioenergetic adaptationMitochondrial metabolismMitochondrial oxygen consumptionMitochondrial numberEnergetic needsMitochondrial adaptationsMitochondrial mechanismsExercise inducesDentate gyrusStratum radiatumSpine synapsesCA1 regionGlial morphologyHippocampal formationNeuronal activityGranule cellsAction potentialsNeuronal morphologyMRNA expression
2006
Ghrelin controls hippocampal spine synapse density and memory performance
Diano S, Farr SA, Benoit SC, McNay EC, da Silva I, Horvath B, Gaskin FS, Nonaka N, Jaeger LB, Banks WA, Morley JE, Pinto S, Sherwin RS, Xu L, Yamada KA, Sleeman MW, Tschöp MH, Horvath TL. Ghrelin controls hippocampal spine synapse density and memory performance. Nature Neuroscience 2006, 9: 381-388. PMID: 16491079, DOI: 10.1038/nn1656.Peer-Reviewed Original ResearchConceptsHippocampal spine synapse densitySpine synapse densitySpine synapse formationGrowth hormone releaseNovel therapeutic strategiesLong-term potentiationHigher brain functionsEnhanced spatial learningGut hormonesGhrelin administrationHypothalamic actionSynapse densitySpine synapsesCA1 regionHormone releaseNeuropeptide ghrelinGhrelin bindingHippocampal formationTherapeutic strategiesMelanocortin systemGhrelinBrain areasMetabolic controlSynaptic changesSynaptic plasticity
2004
Presynaptic N‐methyl‐D‐aspartate receptor expression is increased by estrogen in an aromatase‐rich area of the songbird hippocampus
Saldanha CJ, Schlinger BA, Micevych PE, Horvath TL. Presynaptic N‐methyl‐D‐aspartate receptor expression is increased by estrogen in an aromatase‐rich area of the songbird hippocampus. The Journal Of Comparative Neurology 2004, 469: 522-534. PMID: 14755533, DOI: 10.1002/cne.11035.Peer-Reviewed Original ResearchConceptsHP neuronsVertebrate hippocampusSongbird hippocampusN-methyl-d-aspartate receptor expressionSubcellular characteristicsInfluence of estrogenFunctional plasticityType glutamate receptorsZebra finch brainPrecise mechanismSomal sizeExcitatory pathwaysReceptor expressionExcitatory neurotransmissionExcitatory synapsesGlutamate receptorsPostsynaptic locusPresynaptic boutonsHippocampusEstrogenKey interfacePlasticityNeuronsAromataseAutoreception
2003
Uncoupling Protein 2 Prevents Neuronal Death Including that Occurring during Seizures: A Mechanism for Preconditioning
Diano S, Matthews RT, Patrylo P, Yang L, Beal MF, Barnstable CJ, Horvath TL. Uncoupling Protein 2 Prevents Neuronal Death Including that Occurring during Seizures: A Mechanism for Preconditioning. Endocrinology 2003, 144: 5014-5021. PMID: 12960023, DOI: 10.1210/en.2003-0667.Peer-Reviewed Original ResearchConceptsFree radical-induced cell deathFree radical-induced damageCell deathSeizure inductionSeizure activityNeuronal deathRadical-induced damageTransgenic miceNeurodegenerative disordersCellular stressRobust reductionUCP2 levelsParallel decreaseDeathATP levelsPC12 cellsProtein 2Mitochondrial uncoupling proteinUCP2Mitochondrial numberCellular energy productionFree radicalsHarmful effectsUncoupling proteinEpilepsy
2000
Hormonal regulation of hippocampal spine synapse density involves subcortical mediation
Leranth C, Shanabrough M, Horvath TL. Hormonal regulation of hippocampal spine synapse density involves subcortical mediation. Neuroscience 2000, 101: 349-356. PMID: 11074158, DOI: 10.1016/s0306-4522(00)00369-9.Peer-Reviewed Original ResearchConceptsFimbria/fornix transectionSpine synapse densitySpine densitySynapse densityHippocampal spine synapse densitySubcortical structuresSubcortical mediationPyramidal cell spinesFornix transectionHippocampal CA1 subfieldHippocampal synaptic plasticityCA1 pyramidal cellsFimbria/fornixLong-term potentiationEstrogen replacementIpsilateral hippocampusContralateral hippocampusCA1 subfieldMedian raphePyramidal cellsSupramammillary areaAfferent connectionsHippocampal morphologySeptal complexNew synapses