Featured Publications
ATP Synthase c-Subunit Leak Causes Aberrant Cellular Metabolism in Fragile X Syndrome
Licznerski P, Park HA, Rolyan H, Chen R, Mnatsakanyan N, Miranda P, Graham M, Wu J, Cruz-Reyes N, Mehta N, Sohail S, Salcedo J, Song E, Effman C, Effman S, Brandao L, Xu GN, Braker A, Gribkoff VK, Levy RJ, Jonas EA. ATP Synthase c-Subunit Leak Causes Aberrant Cellular Metabolism in Fragile X Syndrome. Cell 2020, 182: 1170-1185.e9. PMID: 32795412, PMCID: PMC7484101, DOI: 10.1016/j.cell.2020.07.008.Peer-Reviewed Original ResearchConceptsFragile X syndromeC subunitAberrant synaptic developmentHuman fragile X syndromeATP synthase enzymeMental retardation proteinX syndromeATP production efficiencyMRNA translation rateAberrant cellular metabolismATP synthaseMRNA translationTranslation rateCellular metabolismSynaptic growthSynthase enzymeMouse neuronsSynapse maturationSynaptic developmentPharmacological inhibitionLeak channelsSynaptic maturationMembrane leakMaturationMetabolismInefficient thermogenic mitochondrial respiration due to futile proton leak in a mouse model of fragile X syndrome
Griffiths KK, Wang A, Wang L, Tracey M, Kleiner G, Quinzii CM, Sun L, Yang G, Perez‐Zoghbi J, Licznerski P, Yang M, Jonas EA, Levy RJ. Inefficient thermogenic mitochondrial respiration due to futile proton leak in a mouse model of fragile X syndrome. The FASEB Journal 2020, 34: 7404-7426. PMID: 32307754, PMCID: PMC7692004, DOI: 10.1096/fj.202000283rr.Peer-Reviewed Original ResearchConceptsFragile X syndromeProton leakMental retardation protein (FMRP) expressionInefficient oxidative phosphorylationX syndromeCoenzyme Q deficiencyThermogenic respirationMitochondrial CoQTranscriptional silencingFMRP deficiencyFmr1 knockout miceQ deficiencyDysfunctional mitochondriaFMR1 geneFXS phenotypeOxidative phosphorylationMitochondrial respirationCommon genetic causeProtein synthesisFull mutationKey phenotypicPeak of synaptogenesisMitochondriaProtein expressionGenetic causeAlpha-tocotrienol enhances arborization of primary hippocampal neurons via upregulation of Bcl-xL
Park HA, Crowe-White KM, Ciesla L, Scott M, Bannerman S, Davis AU, Adhikari B, Burnett G, Broman K, Ferdous KA, Lackey KH, Licznerski P, Jonas EA. Alpha-tocotrienol enhances arborization of primary hippocampal neurons via upregulation of Bcl-xL. Nutrition Research 2022, 101: 31-42. PMID: 35366596, PMCID: PMC9081260, DOI: 10.1016/j.nutres.2022.02.007.Peer-Reviewed Original ResearchConceptsPrimary hippocampal neuronsControl neuronsHippocampal neuronsAlpha-tocotrienolBcl-xLVitamin E familyCerebral ischemiaNeuronal viabilityMature neuronsB cellsNeurite complexityNeuronal functionMitochondrial energy productionBrain developmentCentral mechanismsNeuronsBeneficial effectsOxidative stressBcl-xL upregulationProtein levelsNeurite branchingTreatmentE familyATP levelsNeurite outgrowthAlpha-Tocotrienol Prevents Oxidative Stress-Mediated Post-Translational Cleavage of Bcl-xL in Primary Hippocampal Neurons
Park HA, Mnatsakanyan N, Broman K, Davis AU, May J, Licznerski P, Crowe-White KM, Lackey KH, Jonas EA. Alpha-Tocotrienol Prevents Oxidative Stress-Mediated Post-Translational Cleavage of Bcl-xL in Primary Hippocampal Neurons. International Journal Of Molecular Sciences 2019, 21: 220. PMID: 31905614, PMCID: PMC6982044, DOI: 10.3390/ijms21010220.Peer-Reviewed Original ResearchConceptsPrimary hippocampal neuronsHippocampal neuronsReactive oxygen speciesMitochondrial dysfunctionBcl-xLMitochondrial membrane potentialMitochondrial functionProduction of ROSExcitotoxic conditionsGlutamate challengeNeuroprotective propertiesMembrane potentialNeuronal deathExcitotoxic stimulationBcl-xL levelsNeuronal survivalIntracellular ATP depletionMitochondrial reactive oxygen speciesB cellsImportant causeDysfunctionNeuronsROS productionATP depletionNeurite outgrowthParkinson’s disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth
Chen R, Park HA, Mnatsakanyan N, Niu Y, Licznerski P, Wu J, Miranda P, Graham M, Tang J, Boon AJW, Cossu G, Mandemakers W, Bonifati V, Smith PJS, Alavian KN, Jonas EA. Parkinson’s disease protein DJ-1 regulates ATP synthase protein components to increase neuronal process outgrowth. Cell Death & Disease 2019, 10: 469. PMID: 31197129, PMCID: PMC6565618, DOI: 10.1038/s41419-019-1679-x.Peer-Reviewed Original ResearchConceptsDJ-1C subunitATP synthaseParkinson's disease protein DJ-1Β-subunitProtein componentsATP synthase β subunitMitochondrial uncouplingDJ-1 bindsATP synthase efficiencyATP synthase F1Synthase β subunitATP production efficiencyProtein DJ-1Neuronal process extensionProtein levelsNeuronal process outgrowthDJ-1 knockoutWild-type counterpartsSubunit protein levelsDJ-1 mutationsSevere defectsCell metabolismKO neuronsKO culturesRemodeling of axo-spinous synapses in the pathophysiology and treatment of depression
Licznerski P, Duman RS. Remodeling of axo-spinous synapses in the pathophysiology and treatment of depression. Neuroscience 2012, 251: 33-50. PMID: 23036622, PMCID: PMC3566360, DOI: 10.1016/j.neuroscience.2012.09.057.Peer-Reviewed Original ResearchConceptsAxo-spinous synapsesAlters spine morphologyPathophysiology of depressionTreatment of depressionLimbic brain regionsEffective therapeutic agentExpression of prePlasticity-related proteinsStress-related illnessesBasic research studiesSynaptic machineryBehavioral deficitsDendritic spinesPsychiatric disordersAnimal modelsFunctional alterationsSynaptic plasticityBrain regionsSpine morphologyPrefrontal cortexTherapeutic agentsStress exposureNeuronal communicationBrain imagingSpine architectureA Bcl-xL–Drp1 complex regulates synaptic vesicle membrane dynamics during endocytosis
Li H, Alavian KN, Lazrove E, Mehta N, Jones A, Zhang P, Licznerski P, Graham M, Uo T, Guo J, Rahner C, Duman RS, Morrison RS, Jonas EA. A Bcl-xL–Drp1 complex regulates synaptic vesicle membrane dynamics during endocytosis. Nature Cell Biology 2013, 15: 773-785. PMID: 23792689, PMCID: PMC3725990, DOI: 10.1038/ncb2791.Peer-Reviewed Original ResearchConceptsBcl-xLVesicle retrievalProtein-protein interactionsClathrin-coated pitsProtein Bcl-xLCalmodulin-dependent mannerRecruitment of vesiclesNeurotransmitter releaseDepletion of Drp1GTPase Drp1Vesicle endocytosisEndocytic vesiclesMembrane dynamicsPlasma membraneClathrin complexMutagenesis studiesPresynaptic plasticityMitochondrial ATPATP availabilityReserve poolDrp1EndocytosisVesiclesHippocampal neuronsComplexesAn uncoupling channel within the c-subunit ring of the F1FO ATP synthase is the mitochondrial permeability transition pore
Alavian KN, Beutner G, Lazrove E, Sacchetti S, Park HA, Licznerski P, Li H, Nabili P, Hockensmith K, Graham M, Porter GA, Jonas EA. An uncoupling channel within the c-subunit ring of the F1FO ATP synthase is the mitochondrial permeability transition pore. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 10580-10585. PMID: 24979777, PMCID: PMC4115574, DOI: 10.1073/pnas.1401591111.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCell DeathHEK293 CellsHumansIon Channel GatingIon ChannelsLiposomesMitochondriaMitochondrial Membrane Transport ProteinsMitochondrial MembranesMitochondrial Permeability Transition PoreMutationProtein ConformationProtein SubunitsProton-Translocating ATPasesRatsReactive Oxygen SpeciesConceptsMitochondrial PT poreF1Fo-ATP synthaseATP synthasePermeability transitionCell deathCellular metabolic efficiencyInner mitochondrial membrane permeabilityOxygen species-induced cell deathC subunit ringATP synthase F1Mitochondrial membrane permeabilityMitochondrial permeability transitionC subunitPT poreTight regulationATP productionMolecular identitySingle-channel conductanceChannel closureLeak channelsMPTP openingMetabolic efficiencyMembrane permeabilityHealthy cellsOsmotic shiftsBcl-xL Is Necessary for Neurite Outgrowth in Hippocampal Neurons
Park HA, Licznerski P, Alavian KN, Shanabrough M, Jonas EA. Bcl-xL Is Necessary for Neurite Outgrowth in Hippocampal Neurons. Antioxidants & Redox Signaling 2015, 22: 93-108. PMID: 24787232, PMCID: PMC4281845, DOI: 10.1089/ars.2013.5570.Peer-Reviewed Original ResearchConceptsDeath receptor 6Hippocampal neuronsNeurite outgrowthExacerbation of hypoxiaBcl-xLNeuronal outgrowthNeuronal process outgrowthNeuronal injuryNeurodegenerative stimuliVivo ischemiaHypoxic injuryNeuronal survivalBrain injuryImpairs neurite outgrowthHypoxic controlsSynapse numberAxonal pruningNeurite damageB cellsReceptor 6Synaptic plasticityDR6 expressionSynapse formationEarly increaseNeuronsDecreased SGK1 Expression and Function Contributes to Behavioral Deficits Induced by Traumatic Stress
Licznerski P, Duric V, Banasr M, Alavian KN, Ota KT, Kang HJ, Jonas EA, Ursano R, Krystal JH, Duman RS, . Decreased SGK1 Expression and Function Contributes to Behavioral Deficits Induced by Traumatic Stress. PLOS Biology 2015, 13: e1002282. PMID: 26506154, PMCID: PMC4623974, DOI: 10.1371/journal.pbio.1002282.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsBehavior, AnimalCohort StudiesDendritic SpinesDepressive Disorder, MajorEnzyme RepressionFemaleGene Transfer TechniquesHippocampusHumansImmediate-Early ProteinsMaleMiddle AgedNerve Tissue ProteinsNeuronsPrefrontal CortexProtein Serine-Threonine KinasesRats, Sprague-DawleySignal TransductionStress Disorders, Post-TraumaticSynaptic TransmissionTissue BanksConceptsMajor depressive disorderPost-traumatic stress disorderPrefrontal cortexAbnormal dendritic spine morphologyCorticolimbic brain regionsAnhedonic-like behaviorInhibition of SGK1Dendritic spine morphologyKinase 1 expressionAmygdala of individualsTraumatic stressPostmortem prefrontal cortexSynaptic dysfunctionDepressive disorderBehavioral deficitsRodent modelsPTSD subjectsFunctional alterationsBrain regionsSGK1 expressionSpine morphologyStress disorderFunction contributesBehavioral changesDisordersDecreased expression of synapse-related genes and loss of synapses in major depressive disorder
Kang HJ, Voleti B, Hajszan T, Rajkowska G, Stockmeier CA, Licznerski P, Lepack A, Majik MS, Jeong LS, Banasr M, Son H, Duman RS. Decreased expression of synapse-related genes and loss of synapses in major depressive disorder. Nature Medicine 2012, 18: 1413-1417. PMID: 22885997, PMCID: PMC3491115, DOI: 10.1038/nm.2886.Peer-Reviewed Original ResearchMeSH KeywordsAnalysis of VarianceAnimalsCalmodulinCell LineDepressive Disorder, MajorGATA1 Transcription FactorGene Expression ProfilingGene Expression RegulationHumansMicroarray AnalysisMicroscopy, ElectronPrefrontal CortexRab3A GTP-Binding ProteinRab4 GTP-Binding ProteinsRatsReverse Transcriptase Polymerase Chain ReactionSynapsesSynapsinsTubulinNeuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress
Son H, Banasr M, Choi M, Chae SY, Licznerski P, Lee B, Voleti B, Li N, Lepack A, Fournier NM, Lee KR, Lee IY, Kim J, Kim JH, Kim YH, Jung SJ, Duman RS. Neuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 11378-11383. PMID: 22733766, PMCID: PMC3396528, DOI: 10.1073/pnas.1201191109.Peer-Reviewed Original ResearchConceptsChronic unpredictable stressAntidepressant actionAtrophy of dendritesDepressive-like behaviorAntidepressant treatment responseSymptoms of depressionExpression of neuritinActivity-dependent genesAntidepressant treatmentLimbic structuresHippocampal expressionUnpredictable stressTreatment responseMood disordersBehavioral deficitsNeuronal plasticityTreatment reversesAnxiety behaviorChronic stressNeuritinDendrite branchingUnique actionHippocampusNeuroplasticityModel of stressActin/α-Actinin-Dependent Transport of AMPA Receptors in Dendritic Spines: Role of the PDZ-LIM Protein RIL
Schulz TW, Nakagawa T, Licznerski P, Pawlak V, Kolleker A, Rozov A, Kim J, Dittgen T, Köhr G, Sheng M, Seeburg PH, Osten P. Actin/α-Actinin-Dependent Transport of AMPA Receptors in Dendritic Spines: Role of the PDZ-LIM Protein RIL. Journal Of Neuroscience 2004, 24: 8584-8594. PMID: 15456832, PMCID: PMC6729893, DOI: 10.1523/jneurosci.2100-04.2004.Peer-Reviewed Original ResearchConceptsAMPA receptorsDendritic spinesLIM domain-containing proteinsDomain-containing proteinsActin-dependent mannerCultured neuronsPostsynaptic density fractionSynaptic AMPA receptorsLIM domainsPDZ domainProtein complexesActin cytoskeletonC-terminal peptideNovel regulationHeterologous cellsReceptor transportRILsExcitatory transmissionForebrain synaptosomesMiniature EPSCsSynaptic accumulationRat forebrainSynaptic sitesSynaptic surfaceReceptorsLentivirus-based genetic manipulations of cortical neurons and their optical and electrophysiological monitoring in vivo
Dittgen T, Nimmerjahn A, Komai S, Licznerski P, Waters J, Margrie TW, Helmchen F, Denk W, Brecht M, Osten P. Lentivirus-based genetic manipulations of cortical neurons and their optical and electrophysiological monitoring in vivo. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 18206-18211. PMID: 15608064, PMCID: PMC539748, DOI: 10.1073/pnas.0407976101.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 2Calcium-Calmodulin-Dependent Protein KinasesElectrophysiologyGenetic VectorsGreen Fluorescent ProteinsHippocampusImage Processing, Computer-AssistedLentivirusMiceMice, Inbred C57BLMicroscopyNeuronsPhenotypePhotonsPromoter Regions, GeneticRecombinant ProteinsRNA, Small InterferingRNA, Small NuclearSynapsinsConceptsU6 promoter-driven expressionMicroscopy-based techniquesGenetic manipulationGene deliveryLentiviral vectorsGene functionGene knockdownSubsequent phenotypic analysisPromoter-driven expressionCellular response propertiesSmall networksTwo-photon microscopyTwo-photon time-lapse imagingCortical neuronsEfficient meansMicroscopyAlpha-calcium/calmodulin-dependent protein kinase IIPostsynaptic excitability is necessary for strengthening of cortical sensory responses during experience-dependent development
Komai S, Licznerski P, Cetin A, Waters J, Denk W, Brecht M, Osten P. Postsynaptic excitability is necessary for strengthening of cortical sensory responses during experience-dependent development. Nature Neuroscience 2006, 9: 1125-1133. PMID: 16921372, DOI: 10.1038/nn1752.Peer-Reviewed Original ResearchConceptsSomatodendritic excitabilityExperience-dependent developmentLayer 2/3 pyramidal neuronsCortical networksSensory responsesRat somatosensory cortexNormal cortical developmentCortical sensory responsesDevelopmental strengtheningPostsynaptic excitabilityPyramidal neuronsSomatosensory cortexCortical neuronsBarrel cortexPostsynaptic neuronsCortical developmentSensory cortexSensory pathwaysSensory responsivenessSynaptic strengthExcitabilitySensory deprivationCortexNeuronsVivo recordingsSelect Overexpression of Homer1a in Dorsal Hippocampus Impairs Spatial Working Memory
Celikel T, Marx V, Freudenberg F, Zivkovic A, Resnik E, Hasan MT, Licznerski P, Osten P, Rozov A, Seeburg PH, Schwarz MK. Select Overexpression of Homer1a in Dorsal Hippocampus Impairs Spatial Working Memory. Frontiers In Neuroscience 2007, 1: 97-110. PMID: 18982121, PMCID: PMC2518050, DOI: 10.3389/neuro.01.1.1.007.2007.Peer-Reviewed Original ResearchLong-term potentiationSynaptic plasticityCA3-CA1 long-term potentiationLong Homer isoformsPostsynaptic excitatory neuronsSpatial working memoryOverexpression of Homer1aDorsal hippocampusGlutamate receptorsExcitatory neuronsSynaptic transmissionCortical areasImpairs spatial working memoryHomer isoformsSimilar impairmentHomer1aLong HomersSpatial workingReference memorySpatial memoryHippocampusFunctional competitionImpairmentOverexpressionExpression of VenusIncomplete and Inaccurate Vocal Imitation after Knockdown of FoxP2 in Songbird Basal Ganglia Nucleus Area X
Haesler S, Rochefort C, Georgi B, Licznerski P, Osten P, Scharff C. Incomplete and Inaccurate Vocal Imitation after Knockdown of FoxP2 in Songbird Basal Ganglia Nucleus Area X. PLOS Biology 2007, 5: e321. PMID: 18052609, PMCID: PMC2100148, DOI: 10.1371/journal.pbio.0050321.Peer-Reviewed Original ResearchConceptsDevelopmental verbal dyspraxiaVocal imitationKnockdown of FoxP2Comprehension of grammarVocal motor learningSong learningWord productionMutations of FOXP2Neural parallelsLanguage disordersHuman speechHuman languageMotor learningFluent productionVerbal dyspraxiaSong ontogenyTutor songSpeechImitationBasal ganglia structuresAcoustic structureLearningGanglia structuresBasal gangliaFoxP2 levelsThe transcription factor orthodenticle homeobox 2 influences axonal projections and vulnerability of midbrain dopaminergic neurons
Chung CY, Licznerski P, Alavian KN, Simeone A, Lin Z, Martin E, Vance J, Isacson O. The transcription factor orthodenticle homeobox 2 influences axonal projections and vulnerability of midbrain dopaminergic neurons. Brain 2010, 133: 2022-2031. PMID: 20573704, PMCID: PMC2892944, DOI: 10.1093/brain/awq142.Peer-Reviewed Original ResearchConceptsMidbrain dopaminergic neuronsVentral mesencephalic culturesTranscription factor orthodenticle homeobox 2Orthodenticle homeobox 2Dopaminergic neuronsMesencephalic culturesShort hairpin RNAHomeobox 2A10 dopaminergic neuronsCyclase-activating peptideHairpin RNAConditional knockout miceVentral mesencephalonNeuronal vulnerabilityDopaminergic projectionsAxonal projectionsParkinson's diseaseAdult miceKnockout miceMN9D cellsNeuropilin-2Elevated geneNeuronsNeuropilin-1Human midbrainA negative regulator of MAP kinase causes depressive behavior
Duric V, Banasr M, Licznerski P, Schmidt HD, Stockmeier CA, Simen AA, Newton SS, Duman RS. A negative regulator of MAP kinase causes depressive behavior. Nature Medicine 2010, 16: 1328-1332. PMID: 20953200, PMCID: PMC3066515, DOI: 10.1038/nm.2219.Peer-Reviewed Original ResearchBDNF signaling: Harnessing stress to battle mood disorder
Licznerski P, Jonas EA. BDNF signaling: Harnessing stress to battle mood disorder. Proceedings Of The National Academy Of Sciences Of The United States Of America 2018, 115: 3742-3744. PMID: 29592951, PMCID: PMC5899500, DOI: 10.1073/pnas.1803645115.Peer-Reviewed Original Research