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 leakMaturationMetabolismAlpha-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 outgrowthRemodeling 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 neuronsComplexesBcl-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 changesDisordersNeuritin 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 IIThe 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 midbrain