2024
Meningeal lymphatic vessel dysfunction driven by CGRP signaling causes migraine-like pain in mice
Thomas J, Schindler E, Gottschalk C. Meningeal lymphatic vessel dysfunction driven by CGRP signaling causes migraine-like pain in mice. Journal Of Clinical Investigation 2024, 134: e182556. PMID: 39087472, PMCID: PMC11290958, DOI: 10.1172/jci182556.Peer-Reviewed Original ResearchConceptsBlocking CGRP signalingCGRP receptor componentsMigraine-like painCervical lymph nodesGap junction proteinPrimary headache disordersLymphatic vessel dysfunctionAcute migrainePharmacological blockadeLymph nodesHeadache disordersNeurological symptomsJunction proteinsCGRPLymphatic vesselsMeningeal lymphatic vesselsInducible knockoutVessel dysfunctionMigraineReceptor componentsHeadachePainPathophysiologyDysfunctionMiceNav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis
Fu W, Vasylyev D, Bi Y, Zhang M, Sun G, Khleborodova A, Huang G, Zhao L, Zhou R, Li Y, Liu S, Cai X, He W, Cui M, Zhao X, Hettinghouse A, Good J, Kim E, Strauss E, Leucht P, Schwarzkopf R, Guo E, Samuels J, Hu W, Attur M, Waxman S, Liu C. Nav1.7 as a chondrocyte regulator and therapeutic target for osteoarthritis. Nature 2024, 625: 557-565. PMID: 38172636, PMCID: PMC10794151, DOI: 10.1038/s41586-023-06888-7.Peer-Reviewed Original ResearchVoltage-gated sodium channelsOA progressionDorsal root ganglion neuronsStructural joint damagePain relief treatmentHuman OA chondrocytesCommon joint diseaseMultiple mouse modelsNav1.7 blockersPain behaviorGanglion neuronsPharmacological blockadeJoint damageJoint degenerationChannel blockersJoint diseaseOA chondrocytesMouse modelTherapeutic targetOsteoarthritisIntracellular Ca2Nav1.7Nav1.7 channelsGenetic ablationLimited evidence
2023
Immune regulatory roles for Kv1.3 channels in Microglia in Alzheimer’s Disease
Bowen C, Lin Y, Zeng H, Nguyen H, Xiao H, Kumar P, Duong D, Espinosa‐Garcia C, Wulff H, Seyfried N, Rangaraju S. Immune regulatory roles for Kv1.3 channels in Microglia in Alzheimer’s Disease. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.078851.Peer-Reviewed Original ResearchKv1.3 blockadeKv1.3 channelsKv1.3 blockersMouse model of AD pathologyBlockade of Kv1.3Immune regulatory roleWestern blottingAlzheimer's diseaseCMV-Cre miceChannels in vitroPDZ-binding motifPlasma membrane proteinsInhibition in vivoCell type-specificPharmacological blockadeOlder 5XFAD miceCMV-CreFunction of microgliaChannel abundanceKv1.3Mouse modelBiotin ligaseFlow cytometryTrafficking proteinsBiotinylated proteinsNaV1.7: A central role in pain
Waxman S, Dib-Hajj S. NaV1.7: A central role in pain. Neuron 2023, 111: 2615-2617. PMID: 37678164, DOI: 10.1016/j.neuron.2023.08.011.Peer-Reviewed Original ResearchConceptsEndogenous opioidsSodium channel NaPharmacological blockadePain insensitivityLoss of functionChannel NaPainAnalgesiaOpioidsBlockadeCentral role
2021
Mitochondrial cristae-remodeling protein OPA1 in POMC neurons couples Ca2+ homeostasis with adipose tissue lipolysis
Gómez-Valadés AG, Pozo M, Varela L, Boudjadja MB, Ramírez S, Chivite I, Eyre E, Haddad-Tóvolli R, Obri A, Milà-Guasch M, Altirriba J, Schneeberger M, Imbernón M, Garcia-Rendueles AR, Gama-Perez P, Rojo-Ruiz J, Rácz B, Alonso MT, Gomis R, Zorzano A, D’Agostino G, Alvarez CV, Nogueiras R, Garcia-Roves PM, Horvath TL, Claret M. Mitochondrial cristae-remodeling protein OPA1 in POMC neurons couples Ca2+ homeostasis with adipose tissue lipolysis. Cell Metabolism 2021, 33: 1820-1835.e9. PMID: 34343501, PMCID: PMC8432968, DOI: 10.1016/j.cmet.2021.07.008.Peer-Reviewed Original ResearchConceptsProtein OPA1Mitochondrial CaMitochondrial cristae architectureAdipose tissue lipolysisKey metabolic sensorPOMC neuronsCellular metabolic adaptationTissue lipolysisCristae architectureMetabolic sensorNutrient availabilityWhite adipose tissue lipolysisAlpha-melanocyte stimulating hormoneGenetic inactivationNovel axisMitochondrial functionOPA1Metabolic adaptationMitochondrial cristaeDramatic alterationsMutant miceProopiomelanocortin neuronsLipolysis controlWAT lipolysisPharmacological blockadeCaveolae-mediated Tie2 signaling contributes to CCM pathogenesis in a brain endothelial cell-specific Pdcd10-deficient mouse model
Zhou HJ, Qin L, Jiang Q, Murray KN, Zhang H, Li B, Lin Q, Graham M, Liu X, Grutzendler J, Min W. Caveolae-mediated Tie2 signaling contributes to CCM pathogenesis in a brain endothelial cell-specific Pdcd10-deficient mouse model. Nature Communications 2021, 12: 504. PMID: 33495460, PMCID: PMC7835246, DOI: 10.1038/s41467-020-20774-0.Peer-Reviewed Original ResearchConceptsCerebral cavernous malformationsCCM lesionsSmooth muscle actin-positive pericytesEndothelial cell lossRegions of brainCCM pathogenesisPost-capillary venulesCerebral hemorrhagePharmacological blockadeVascular abnormalitiesEC-specific deletionCavernous malformationsMouse modelCell lossMicrovascular bedGenetic deletionLesion formationLesionsVascular dynamicsBarrier functionMicrovascular structureTwo-photon microscopyTie2PathogenesisMicePhotoreceptive Ganglion Cells Drive Circuits for Local Inhibition in the Mouse Retina
Pottackal J, Walsh HL, Rahmani P, Zhang K, Justice NJ, Demb JB. Photoreceptive Ganglion Cells Drive Circuits for Local Inhibition in the Mouse Retina. Journal Of Neuroscience 2021, 41: 1489-1504. PMID: 33397711, PMCID: PMC7896016, DOI: 10.1523/jneurosci.0674-20.2020.Peer-Reviewed Original ResearchMeSH KeywordsAmacrine CellsAnimalsCorticotropin-Releasing HormoneElectrophysiological PhenomenaExcitatory Postsynaptic PotentialsFemalegamma-Aminobutyric AcidGap JunctionsMaleMiceMice, Inbred C57BLNeural InhibitionNeuronsOptogeneticsPhotoreceptor Cells, VertebrateRetinaRetinal Cone Photoreceptor CellsRetinal Ganglion CellsRetinal Rod Photoreceptor CellsRod OpsinsSynapsesConceptsGap junction-mediated electrical synapsesAmacrine cellsElectrical synapsesIpRGC activityGanglion cellsRetinal interneuronsRetinal circuitsPhotosensitive retinal ganglion cellsGABAergic amacrine cellsRetinal ganglion cellsWhole-cell recordingsSpecific RGC typesAbsence of rodsIpRGC typesRGC typesPharmacological blockadeRetinal neuronsMelanopsin expressionMature retinaMouse retinaSynaptic circuitsNeuronal circuitsInterneuronsOptogenetic stimulationLocal inhibition
2020
Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer
Zhang Z, Karthaus W, Lee Y, Gao V, Wu C, Russo J, Liu M, Mota J, Abida W, Linton E, Lee E, Barnes S, Chen H, Mao N, Wongvipat J, Choi D, Chen X, Zhao H, Manova-Todorova K, de Stanchina E, Taplin M, Balk S, Rathkopf D, Gopalan A, Carver B, Mu P, Jiang X, Watson P, Sawyers C. Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer. Cancer Cell 2020, 38: 279-296.e9. PMID: 32679108, PMCID: PMC7472556, DOI: 10.1016/j.ccell.2020.06.005.Peer-Reviewed Original ResearchMeSH KeywordsAndrogen AntagonistsAnimalsCancer-Associated FibroblastsCell Line, TumorCell ProliferationCells, CulturedDrug Resistance, NeoplasmGene Expression ProfilingGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateMaleMice, SCIDNeuregulin-1Prostatic NeoplasmsTumor MicroenvironmentXenograft Model Antitumor AssaysConceptsCancer-associated fibroblastsProstate cancerAntiandrogen resistanceNeuregulin-1Second-generation antiandrogen therapyResistance to hormonal therapyCastration-resistant prostate cancerTreat advanced prostate cancerProstate organoid culturesSecond-generation antiandrogensAdvanced prostate cancerActivation of HER3Antiandrogen therapyHormone therapyHormone deprivationPharmacological blockadeTargeted therapyParacrine mechanismsTumor cellsMouse modelProstateClinical testingOrganoid culturesTherapyCancerLoss of p53 drives neuron reprogramming in head and neck cancer
Amit M, Takahashi H, Dragomir MP, Lindemann A, Gleber-Netto FO, Pickering CR, Anfossi S, Osman AA, Cai Y, Wang R, Knutsen E, Shimizu M, Ivan C, Rao X, Wang J, Silverman DA, Tam S, Zhao M, Caulin C, Zinger A, Tasciotti E, Dougherty PM, El-Naggar A, Calin GA, Myers JN. Loss of p53 drives neuron reprogramming in head and neck cancer. Nature 2020, 578: 449-454. PMID: 32051587, PMCID: PMC9723538, DOI: 10.1038/s41586-020-1996-3.Peer-Reviewed Original ResearchMeSH KeywordsAdrenergic AntagonistsAdrenergic NeuronsAnimalsCell DivisionCell TransdifferentiationCellular ReprogrammingDisease Models, AnimalDisease ProgressionFemaleHumansMaleMiceMice, Inbred BALB CMicroRNAsMouth NeoplasmsNerve FibersNeuritesReceptors, AdrenergicRetrospective StudiesSensory Receptor CellsTumor MicroenvironmentTumor Suppressor Protein p53Xenograft Model Antitumor AssaysConceptsOral cancerNerve fibersAdrenergic nerve fibersPoor clinical outcomeTrigeminal sensory neuronsLoss of TP53Sensory denervationAdrenergic nervesChemical sympathectomyNerve densitySensory nervesClinical outcomesSolid tumor microenvironmentLoss of p53Neck cancerPharmacological blockadeEndogenous neuronsRetrospective analysisMouse modelSensory neuronsAdrenergic phenotypeAdrenergic receptorsTumor growthTumor progressionTumor microenvironment
2017
mTOR (Mechanistic Target of Rapamycin) Inhibition Decreases Mechanosignaling, Collagen Accumulation, and Stiffening of the Thoracic Aorta in Elastin-Deficient Mice
Jiao Y, Li G, Li Q, Ali R, Qin L, Li W, Qyang Y, Greif DM, Geirsson A, Humphrey JD, Tellides G. mTOR (Mechanistic Target of Rapamycin) Inhibition Decreases Mechanosignaling, Collagen Accumulation, and Stiffening of the Thoracic Aorta in Elastin-Deficient Mice. Arteriosclerosis Thrombosis And Vascular Biology 2017, 37: 1657-1666. PMID: 28751568, PMCID: PMC5574180, DOI: 10.1161/atvbaha.117.309653.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAorta, ThoracicAortic DiseasesCell ProliferationCollagenElastinEverolimusFocal Adhesion Kinase 1Genetic Predisposition to DiseaseHumansImatinib MesylateMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2Mechanotransduction, CellularMice, Inbred C57BLMice, KnockoutMultiprotein ComplexesMuscle, Smooth, VascularPhenotypePhosphorylationProtein Kinase InhibitorsSirolimusTime FactorsTOR Serine-Threonine KinasesVascular StiffnessWilliams SyndromeConceptsElastin deficiencyCollagen accumulationArterial phenotypeNull miceGrowth factorSmooth muscle cell proliferationMuscle cell proliferationEarly postnatal deathInhibition of mTORAortic fibrosisAortic obstructionMedial thickeningAortic stiffeningNeonatal deathLuminal stenosisPharmacological blockadeAbsence of elastinThoracic aortaTherapeutic benefitJuvenile micePostnatal deathMTOR inhibitionAortaHeterozygous lossMice
2016
Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer
Yin M, Li X, Tan S, Zhou HJ, Ji W, Bellone S, Xu X, Zhang H, Santin AD, Lou G, Min W. Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer. Journal Of Clinical Investigation 2016, 126: 4157-4173. PMID: 27721235, PMCID: PMC5096908, DOI: 10.1172/jci87252.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsErbB ReceptorsFemaleHeterograftsHumansIntercellular Adhesion Molecule-1Macrophage-1 AntigenMacrophagesMiceMice, NudeNeoplasm MetastasisNeoplasm ProteinsNeoplasm TransplantationOvarian NeoplasmsSpheroids, CellularVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1ConceptsTumor-associated macrophagesOvarian cancerTranscoelomic metastasisTumor cellsICAM-1Mouse modelEpithelial ovarian cancerOvarian cancer growthOvarian cancer metastasisSpheroid formationOvarian cancer progressionVEGF/VEGFRTumor cell proliferationPharmacological blockadeMetastatic cancerColon cancerCancer growthMetastasisAntibody neutralizationTumor growthCancerClinical pathologyCancer metastasisCancer progressionΑMβ2 integrin
2013
Nitric Oxide and TNFα Are Critical Regulators of Reversible Lymph Node Vascular Remodeling and Adaptive Immune Response
Sellers SL, Iwasaki A, Payne GW. Nitric Oxide and TNFα Are Critical Regulators of Reversible Lymph Node Vascular Remodeling and Adaptive Immune Response. PLOS ONE 2013, 8: e60741. PMID: 23573281, PMCID: PMC3616017, DOI: 10.1371/journal.pone.0060741.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAnimalsArteriolesCell DegranulationChlorocebus aethiopsFemaleHerpes SimplexLymph NodesMast CellsMiceMice, 129 StrainMice, Inbred C57BLMice, KnockoutNeovascularization, PhysiologicNG-Nitroarginine Methyl EsterNifedipineNitric OxideNitric Oxide Synthase Type IIIPhenylephrineTumor Necrosis Factor-alphaVasoconstrictionVasodilator AgentsVero CellsConceptsAdaptive immune responsesEndothelial nitric oxide synthaseImmune responseVascular remodelingHerpes simplex type II infectionT cell-dependent mechanismGenetic ablation modelCell-dependent mechanismNitric oxide levelsType II infectionNitric oxide synthaseCourse of infectionInguinal LNsLN cellularityVascular eventsVascular changesArteriole diameterPharmacological blockadeMain arterioleOxide synthaseTNFα expressionMast cellsOxide levelsViral infectionIntravital microscopy
2004
Nogo Receptor Antagonism Promotes Stroke Recovery by Enhancing Axonal Plasticity
Lee JK, Kim JE, Sivula M, Strittmatter SM. Nogo Receptor Antagonism Promotes Stroke Recovery by Enhancing Axonal Plasticity. Journal Of Neuroscience 2004, 24: 6209-6217. PMID: 15240813, PMCID: PMC6729662, DOI: 10.1523/jneurosci.1643-04.2004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsBehavior, AnimalDisease Models, AnimalGPI-Linked ProteinsInfarction, Middle Cerebral ArteryMaleMiceMice, KnockoutMyelin ProteinsNeuronal PlasticityNogo ProteinsNogo Receptor 1RatsRats, Sprague-DawleyReceptors, Cell SurfaceReceptors, PeptideRecombinant Fusion ProteinsRecovery of FunctionStrokeTreatment OutcomeConceptsAxonal plasticityStroke recoveryIpsilateral cervical spinal cordMiddle cerebral artery occlusionFocal brain infarctionCerebral artery occlusionCervical spinal cordComplex motor functionContralateral red nucleusUndamaged cortexBrain infarctionArtery occlusionIschemic strokeAxonal sproutingIntracerebroventricular administrationArterial occlusionPharmacological blockadeMotor functionSpinal cordControl animalsRed nucleusAxonal connectionsBehavioral improvementMutant miceStroke
1991
Na+‐Ca2+ exchanger mediates Ca2+ influx during anoxia in mammalian central nervous system white matter
Stys P, Waxman S, Ransom B. Na+‐Ca2+ exchanger mediates Ca2+ influx during anoxia in mammalian central nervous system white matter. Annals Of Neurology 1991, 30: 375-380. PMID: 1952825, DOI: 10.1002/ana.410300309.Peer-Reviewed Original ResearchConceptsWhite matterIsolated rat optic nerveCentral nervous system white matterNervous system white matterWhite matter injuryRat optic nerveMammalian central nervous systemSevere neurological impairmentCompound action potentialType of injuryCentral nervous systemFunctional recoveryOptic nervePharmacological blockadeNeurological impairmentAnoxic injuryIrreversible injuryNervous systemAction potentialsInjuryInfluxCa2Critical mechanismCellsNerve
1987
Physiological properties of regenerated rat sciatic nerve following lesions at different postnatal ages
Bowe C, Kocsis J, Waxman S, Hildebrand C. Physiological properties of regenerated rat sciatic nerve following lesions at different postnatal ages. Brain Research 1987, 34: 123-131. DOI: 10.1016/0165-3806(87)90201-x.Peer-Reviewed Original ResearchControl nervesPostnatal ageSciatic nerveRegenerated nervesRegenerated rat sciatic nerveFrequency-following abilityOlder postnatal ageSciatic crush lesionRegenerated sciatic nerveAge 3 weeksCompound action potentialDifferent postnatal agesRat sciatic nerveWhole-nerve responseMonths of ageRelative refractory periodCrush lesionPharmacological blockadeNerve responsesSlight prolongationNerveElectrophysiological propertiesAction potentialsRefractory periodOlder age
1986
Action potential characteristics of demyelinated rat sciatic nerve following application of 4-aminopyridine
Targ E, Kocsis J. Action potential characteristics of demyelinated rat sciatic nerve following application of 4-aminopyridine. Brain Research 1986, 363: 1-9. PMID: 3004637, DOI: 10.1016/0006-8993(86)90652-9.Peer-Reviewed Original ResearchConceptsAction potentialsSciatic nerveFrequency-following abilityMultiple spike dischargesSite of demyelinationCompound action potentialPotassium channel blockerRat sciatic nerveAction potential characteristicsVariety of abnormalitiesAbsolute refractory periodExcitability changesPharmacological blockadeSpontaneous firingDemyelinated axonsChannel blockersConduction slowingConduction blockSpike dischargesLesion siteRefractory periodExcitability propertiesClinical useAxonsPotassium channels
1985
Differences between mammalian ventral and dorsal spinal roots in response to blockade of potassium channels during maturation
Bowe C, Kocsis J, Waxman S. Differences between mammalian ventral and dorsal spinal roots in response to blockade of potassium channels during maturation. Proceedings Of The Royal Society B 1985, 224: 355-366. PMID: 2410932, DOI: 10.1098/rspb.1985.0037.Peer-Reviewed Original ResearchConceptsDorsal spinal rootsSensory fibersMammalian motorPotassium channelsSpinal rootsAction potentialsRoot fibersCompound action potentialSingle sensory fibresDorsal root fibersVentral root fibersClasses of axonsIndividual action potentialsPharmacological blockadeVentral rootsYoung rootsSensory axonsWhole nervePotassium conductanceAxon responsesCourse of maturationBlockadeAxonsRoots resultsDifferential sensitivity
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