2014
Dynamic-clamp analysis of wild-type human Nav1.7 and erythromelalgia mutant channel L858H
Vasylyev DV, Han C, Zhao P, Dib-Hajj S, Waxman SG. Dynamic-clamp analysis of wild-type human Nav1.7 and erythromelalgia mutant channel L858H. Journal Of Neurophysiology 2014, 111: 1429-1443. PMID: 24401712, DOI: 10.1152/jn.00763.2013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiophysicsCells, CulturedElectric StimulationErythromelalgiaGanglia, SpinalHEK293 CellsHumansMembrane PotentialsMiceMice, KnockoutModels, BiologicalMutationNAV1.7 Voltage-Gated Sodium ChannelNeural ConductionNeuronsPatch-Clamp TechniquesSodium Channel BlockersTetrodotoxinTransfectionConceptsDRG neuronsMutant Nav1.7 channelsNav1.7 channelsDorsal root ganglion neuronsSodium influxPrimary nociceptive neuronsSmall DRG neuronsNet sodium influxSodium channel Nav1.7Current thresholdMechanistic linkAction potential generationNeuropathic painNociceptive neuronsNociceptor functionGanglion neuronsNociceptor hyperexcitabilityPain phenotypesChannel expressionChannel Nav1.7Subthreshold depolarizationHuman Nav1.7Electrophysiological recordingsDynamic-Clamp AnalysisIdentification of gain
2013
Sodium Channels Contribute to Degeneration of Dorsal Root Ganglion Neurites Induced by Mitochondrial Dysfunction in an In Vitro Model of Axonal Injury
Persson AK, Kim I, Zhao P, Estacion M, Black JA, Waxman SG. Sodium Channels Contribute to Degeneration of Dorsal Root Ganglion Neurites Induced by Mitochondrial Dysfunction in an In Vitro Model of Axonal Injury. Journal Of Neuroscience 2013, 33: 19250-19261. PMID: 24305821, PMCID: PMC6618782, DOI: 10.1523/jneurosci.2148-13.2013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAxonsAxotomyCell DeathCells, CulturedGanglia, SpinalHumansHydrogen PeroxideImmunohistochemistryMiceMice, TransgenicMicrotubulesMitochondrial DiseasesNerve DegenerationNeuritesOxidantsRotenoneSodium Channel BlockersSodium ChannelsSodium-Calcium ExchangerSodium-Potassium-Exchanging ATPaseTetrodotoxinThioureaUncoupling AgentsConceptsAxonal degenerationNeurite degenerationSodium channelsKB-R7943Mouse peripheral sensory neuronsRotenone-induced mitochondrial dysfunctionOxidative stressMitochondrial dysfunctionPeripheral sensory neuronsDorsal root gangliaPeripheral nervous systemDegeneration of neuritesMitochondrial functionVoltage-gated sodium channelsMultiple neurodegenerative disordersSodium-calcium exchangerImpaired mitochondrial functionInjurious cascadeAxonal injuryActivity blockadeRoot gangliaAxonal neuropathySensory neuronsNCX activityDysfunctional intracellularSmall-Fiber Neuropathy Nav1.8 Mutation Shifts Activation to Hyperpolarized Potentials and Increases Excitability of Dorsal Root Ganglion Neurons
Huang J, Yang Y, Zhao P, Gerrits MM, Hoeijmakers JG, Bekelaar K, Merkies IS, Faber CG, Dib-Hajj SD, Waxman SG. Small-Fiber Neuropathy Nav1.8 Mutation Shifts Activation to Hyperpolarized Potentials and Increases Excitability of Dorsal Root Ganglion Neurons. Journal Of Neuroscience 2013, 33: 14087-14097. PMID: 23986244, PMCID: PMC6618513, DOI: 10.1523/jneurosci.2710-13.2013.Peer-Reviewed Original ResearchMeSH KeywordsAction PotentialsAmino Acid SequenceAnimalsCells, CulturedGanglia, SpinalHumansIon Channel GatingMaleMembrane PotentialsMiceMice, TransgenicMiddle AgedMolecular Sequence DataMutation, MissenseNAV1.8 Voltage-Gated Sodium ChannelNeuronsPeripheral Nervous System DiseasesRatsRats, Sprague-DawleyConceptsDorsal root ganglion neuronsSmall DRG neuronsDRG neuronsGanglion neuronsAction potentialsIdiopathic small fiber neuropathySmall-diameter DRG neuronsWhole-cell voltage-clamp recordingsSmall-caliber nerve fibersVoltage-gated sodium channel Nav1.7Peripheral sensory neuronsCurrent-clamp studiesLimited treatment optionsSmall fiber neuropathySodium channel Nav1.8Voltage-clamp recordingsSodium channel Nav1.7Autonomic dysfunctionIncreases excitabilityTreatment optionsUnknown etiologyFunctional variantsNerve fibersSensory neuronsRamp depolarization
2011
Rac1-regulated dendritic spine remodeling contributes to neuropathic pain after peripheral nerve injury
Tan AM, Chang YW, Zhao P, Hains BC, Waxman SG. Rac1-regulated dendritic spine remodeling contributes to neuropathic pain after peripheral nerve injury. Experimental Neurology 2011, 232: 222-233. PMID: 21963650, DOI: 10.1016/j.expneurol.2011.08.028.Peer-Reviewed Original ResearchConceptsDorsal horn neuronsPeripheral nerve injuryChronic constriction injuryWide dynamic range dorsal horn neuronsRange dorsal horn neuronsNerve injuryNeuropathic painDendritic spinesTactile allodyniaThermal hyperalgesiaSpine morphologyInjury-induced hyperexcitabilityNoxious peripheral stimuliSpinal cord injuryMushroom-shaped spinesDendritic spine developmentDendritic spine morphologyConstriction injuryHyperexcitable responsesCCI animalsNeuronal hyperexcitabilityIpsilateral hindNociceptive thresholdSpine densityCord injury
2009
BDNF-Hypersecreting Human Mesenchymal Stem Cells Promote Functional Recovery, Axonal Sprouting, and Protection of Corticospinal Neurons after Spinal Cord Injury
Sasaki M, Radtke C, Tan AM, Zhao P, Hamada H, Houkin K, Honmou O, Kocsis JD. BDNF-Hypersecreting Human Mesenchymal Stem Cells Promote Functional Recovery, Axonal Sprouting, and Protection of Corticospinal Neurons after Spinal Cord Injury. Journal Of Neuroscience 2009, 29: 14932-14941. PMID: 19940189, PMCID: PMC2825276, DOI: 10.1523/jneurosci.2769-09.2009.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain-Derived Neurotrophic FactorCells, CulturedCytoprotectionDisease Models, AnimalFemaleGene ExpressionGenetic VectorsGrowth ConesHumansMesenchymal Stem Cell TransplantationNerve RegenerationNeuronal PlasticityPyramidal TractsRatsRats, Sprague-DawleyRecovery of FunctionSpinal Cord InjuriesTransfectionTransplantation, HeterologousTreatment OutcomeConceptsSpinal cord injuryMesenchymal stem cellsCord injuryFunctional outcomeBone marrowAcute spinal cord injuryBrain-derived neurotrophic factorCorticospinal tract neuronsNumber of FGImproved functional outcomesPrimary motor cortexSpinal gray matterPotential therapeutic effectsStem cellsM1 cortexTransection lesionCorticospinal neuronsTract neuronsAxonal sproutingFunctional recoveryVentral hornNeuronal densitySerotonergic fibersLesion cavityMotor cortex
2007
Anisomycin protects cortical neurons from prolonged hypoxia with differential regulation of p38 and ERK
Hong SS, Qian H, Zhao P, Bazzy-Asaad A, Xia Y. Anisomycin protects cortical neurons from prolonged hypoxia with differential regulation of p38 and ERK. Brain Research 2007, 1149: 76-86. PMID: 17391655, PMCID: PMC1937507, DOI: 10.1016/j.brainres.2007.02.062.Peer-Reviewed Original ResearchConceptsDOR inhibitionCortical neuronsP38 immunoreactivityNeuronal injuryNeuronal responsesMAP kinase activityDelta opioid receptor signalingCultured cortical neuronsHypoxia-induced injuryNormoxic neuronsMAP kinaseNeuronal survivalNeuronal viabilitySurvival/deathSignificant injuryInjuryNaltrindoleCell survival/deathPhosphorylated p38Receptor signalingNeuronsImmunoreactivityHypoxiaPhosphorylated ERKLDH leakage
2006
Rapid Hypoxia Preconditioning Protects Cortical Neurons From Glutamate Toxicity Through δ-Opioid Receptor
Zhang J, Qian H, Zhao P, Hong SS, Xia Y. Rapid Hypoxia Preconditioning Protects Cortical Neurons From Glutamate Toxicity Through δ-Opioid Receptor. Stroke 2006, 37: 1094-1099. PMID: 16514101, DOI: 10.1161/01.str.0000206444.29930.18.Peer-Reviewed Original ResearchConceptsDelta-opioid receptorsHypoxia preconditioningCortical neuronsNeuronal injuryGlutamate-induced neuronal injuryCultured rat cortical neuronsReceptor bindingSevere hypoxic injurySevere neuronal injuryRT-PCRCultured cortical neuronsMRNA levelsNMDA receptor expressionRat cortical neuronsΔ-opioid receptorsDOR mRNA levelsCulture day 8Short-term hypoxiaDOR mRNALactate dehydrogenase leakageHypoxic injuryGlutamate toxicityNeuronal viabilityReceptor expressionNeuroprotection
2005
GABA and glycine are protective to mature but toxic to immature rat cortical neurons under hypoxia
Zhao P, Qian H, Xia Y. GABA and glycine are protective to mature but toxic to immature rat cortical neurons under hypoxia. European Journal Of Neuroscience 2005, 22: 289-300. PMID: 16045482, DOI: 10.1111/j.1460-9568.2005.04222.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCell CountCell DeathCell DifferentiationCell HypoxiaCells, CulturedCerebral CortexDose-Response Relationship, DrugDrug InteractionsEmbryo, MammalianEnkephalin, Leucine-2-AlanineGamma-Aminobutyric AcidGene Expression Regulation, DevelopmentalGlycineL-Lactate DehydrogenaseNeuronsRatsRats, Sprague-DawleyReceptors, GABA-AReceptors, GlycineReference ValuesTaurineTime FactorsConceptsGamma-aminobutyric acidRat cortical neuronsCortical neuronsInhibitory neurotransmitterHypoxic neuronsImmature neuronsHypoxic cortical neuronsDelta-opioid receptorsMajor inhibitory neurotransmitterHypoxic injuryNeuronal ageMature neuronsNeuronal responsesGlycine receptorsLong-term exposureNeuronsDifferential developmental profilesHypoxiaNeurotransmittersDevelopmental profileReceptorsTaurinePresent studyAgeRecent studiesOxygen-sensitive δ-Opioid Receptor-regulated Survival and Death Signals NOVEL INSIGHTS INTO NEURONAL PRECONDITIONING AND PROTECTION*
Ma M, Qian H, Ghassemi F, Zhao P, Xia Y. Oxygen-sensitive δ-Opioid Receptor-regulated Survival and Death Signals NOVEL INSIGHTS INTO NEURONAL PRECONDITIONING AND PROTECTION*. Journal Of Biological Chemistry 2005, 280: 16208-16218. PMID: 15687501, DOI: 10.1074/jbc.m408055200.Peer-Reviewed Original ResearchConceptsDelta-opioid receptorsHPC protectionSevere hypoxiaSpecific signaling pathwaysCytochrome c releaseP38 MAPK activityKinase C pathwayBcl-2 activityMembrane proteinsC releaseMAPK activityMolecular mechanismsSignaling pathwaysΔ-opioid receptorsP38 MAPKNovel insightsNovel mechanismC pathwayNeuronal injuryDOR antagonistDOR mRNAProtein levelsDOR expressionIschemic disordersNeuronal preconditioning
2002
Neuroprotective role of δ-opioid receptors in cortical neurons
Zhang J, Gibney GT, Zhao P, Xia Y. Neuroprotective role of δ-opioid receptors in cortical neurons. American Journal Of Physiology - Cell Physiology 2002, 282: c1225-c1234. PMID: 11997236, DOI: 10.1152/ajpcell.00226.2001.Peer-Reviewed Original ResearchConceptsCortical neuronsNeuronal injuryHypoxic injuryReceptor activationKappa-opioid receptor inhibitionDelta-opioid receptor activationOpioid receptor activationCultured cortical neuronsGlutamate-induced injuryΔ-opioid receptorsLactate dehydrogenase releaseImmature neuronsNeuroprotective roleReceptor inhibitionHypoxic exposureNeuronal susceptibilityCell injuryDay 4InjuryDehydrogenase releaseNeuronsActivation/inhibitionHypoxiaHypoxic conditionsHypoxic stress