Milan Stoiljkovic, MD, PhD
Cards
About
Research
Publications
2023
Response to: Elevated L1 expression in ataxia telangiectasia likely explained by an RNA-seq batch effect
Takahashi T, Stoiljkovic M, Song E, Gao X, Yasumoto Y, Kudo E, Carvalho F, Kong Y, Park A, Shanabrough M, Szigeti-Buck K, Liu Z, Kristant A, Zhang Y, Sulkowski P, Glazer P, Kaczmarek L, Horvath T, Iwasaki A. Response to: Elevated L1 expression in ataxia telangiectasia likely explained by an RNA-seq batch effect. Neuron 2023, 111: 612-613. PMID: 36863323, DOI: 10.1016/j.neuron.2023.02.006.Peer-Reviewed Original Research
2022
LINE-1 activation in the cerebellum drives ataxia
Takahashi T, Stoiljkovic M, Song E, Gao XB, Yasumoto Y, Kudo E, Carvalho F, Kong Y, Park A, Shanabrough M, Szigeti-Buck K, Liu ZW, Kristant A, Zhang Y, Sulkowski P, Glazer PM, Kaczmarek LK, Horvath TL, Iwasaki A. LINE-1 activation in the cerebellum drives ataxia. Neuron 2022, 110: 3278-3287.e8. PMID: 36070749, PMCID: PMC9588660, DOI: 10.1016/j.neuron.2022.08.011.Peer-Reviewed Original ResearchConceptsLINE-1 activationL1 activationAtaxia telangiectasia patientsNuclear element-1Transposable elementsEpigenetic silencersHuman genomeL1 promoterMolecular regulatorsDNA damagePurkinje cell dysfunctionElement 1First direct evidenceTelangiectasia patientsDirect targetingCerebellar expressionNeurodegenerative diseasesDisease etiologyCalcium homeostasisAgRP neurons control structure and function of the medial prefrontal cortex
Stutz B, Waterson MJ, Šestan-Peša M, Dietrich MO, Škarica M, Sestan N, Racz B, Magyar A, Sotonyi P, Liu ZW, Gao XB, Matyas F, Stoiljkovic M, Horvath TL. AgRP neurons control structure and function of the medial prefrontal cortex. Molecular Psychiatry 2022, 27: 3951-3960. PMID: 35906488, PMCID: PMC9891653, DOI: 10.1038/s41380-022-01691-8.Peer-Reviewed Original ResearchConceptsMedial prefrontal cortexAgRP neuronsNon-selective dopamine receptor antagonistBrain functionPrefrontal cortexHypothalamic AgRP neuronsMedial thalamic neuronsAdministration of clozapineDopamine receptor antagonistVentral tegmental areaOscillatory network activityHigher-order brain functionsHypothalamic agoutiThalamic neuronsChemogenetic inhibitionDopaminergic neuronsReceptor antagonistTegmental areaNeuronal pathwaysSensorimotor gatingAdult miceModulatory impactAmbulatory behaviorConstitutive impairmentNeuronsTREM2 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 speciesCerebellar Kv3.3 potassium channels activate TANK-binding kinase 1 to regulate trafficking of the cell survival protein Hax-1
Zhang Y, Varela L, Szigeti-Buck K, Williams A, Stoiljkovic M, Šestan-Peša M, Henao-Mejia J, D’Acunzo P, Levy E, Flavell RA, Horvath TL, Kaczmarek LK. Cerebellar Kv3.3 potassium channels activate TANK-binding kinase 1 to regulate trafficking of the cell survival protein Hax-1. Nature Communications 2021, 12: 1731. PMID: 33741962, PMCID: PMC7979925, DOI: 10.1038/s41467-021-22003-8.Peer-Reviewed Original ResearchConceptsTank Binding Kinase 1HAX-1Kv3.3 potassium channelMultivesicular bodiesKinase 1TANK-binding kinase 1Activation of caspasesAnti-apoptotic proteinsPotassium channelsMembrane proteinsBiochemical pathwaysCerebellar neuronsChannels bindCell deathTBK1 activityIon channelsMutant channelsCellular constituentsTraffickingKv3.3 channelsProteinNeuronal survivalMutationsChannel inactivationCaspasesTherapy 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
2020
Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice
Tan Y, Hang F, Liu ZW, Stoiljkovic M, Wu M, Tu Y, Han W, Lee AM, Kelley C, Hajos M, Lu L, de Lecea L, de Araujo I, Picciotto M, Horvath TL, Gao XB. Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice. Journal Of Clinical Investigation 2020, 130: 4985-4998. PMID: 32516139, PMCID: PMC7456212, DOI: 10.1172/jci130889.Peer-Reviewed Original ResearchConceptsHcrt cellsObese miceDiet-induced obese miceObese male miceExcessive energy intakeNeuropeptide hypocretin/orexinHypocretin/orexinHcrt neuronsMale miceHcrt systemClinical studiesCommon causeSynaptic transmissionObese animalsEnergy intakeAcute stressCognitive functionSalient stimuliAlters responsesExact mechanismMiceHomeostatic regulationNeuronal networksBehavioral changesNeurons
2019
Age-dependent emergence of neurophysiological and behavioral abnormalities in progranulin-deficient mice
Nagy D, Martens LH, Leventhal L, Chen A, Kelley C, Stoiljkovic M, Hajós M. Age-dependent emergence of neurophysiological and behavioral abnormalities in progranulin-deficient mice. Alzheimer's Research & Therapy 2019, 11: 88. PMID: 31639062, PMCID: PMC6805349, DOI: 10.1186/s13195-019-0540-x.Peer-Reviewed Original ResearchConceptsHomozygous miceProgranulin deficiencyBehavioral abnormalitiesFrontotemporal dementiaAge-dependent emergenceHuman frontotemporal dementiasProgranulin-deficient miceExtensive neuronal lossAge-dependent deficitsPaired-pulse depressionHeterogeneous neurodegenerative disorderNeuronal lossVivo electrophysiologyCortical pathwaysThalamocortical circuitsTemporal lobeSynaptic connectivityBehavioral alterationsConclusionOur findingsNeurodegenerative disordersMiceFunction mutationsAge 3DementiaAbnormalities
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 effectiveness