2023
Cx26 heterozygous mutations cause hyperacusis-like hearing oversensitivity and increase susceptibility to noise
Liu L, Liang C, Chen J, Fang S, Zhao H. Cx26 heterozygous mutations cause hyperacusis-like hearing oversensitivity and increase susceptibility to noise. Science Advances 2023, 9: eadf4144. PMID: 36753545, PMCID: PMC9908021, DOI: 10.1126/sciadv.adf4144.Peer-Reviewed Original ResearchConceptsActive cochlear amplificationCochlear amplificationHeterozygous mutationsPermanent hearing threshold shiftHearing threshold shiftCochlear lateral wallNonsyndromic hearing lossHearing lossMouse modelGeneral populationNoise exposureThreshold shiftHeterozygote carriersHearing sensitivityLateral wallJunction genesGap junction genesPotential generationUnexpected findingExposureMutationsOversensitivityProtein prestinDeafness
2021
Efferent neurons control hearing sensitivity and protect hearing from noise through the regulation of gap junctions between cochlear supporting cells
Zhao H, Liu L, Yu N, Zhu Y, Mei L, Chen J, Liang C. Efferent neurons control hearing sensitivity and protect hearing from noise through the regulation of gap junctions between cochlear supporting cells. Journal Of Neurophysiology 2021, 127: 313-327. PMID: 34907797, PMCID: PMC8759971, DOI: 10.1152/jn.00468.2021.Peer-Reviewed Original ResearchConceptsOuter hair cellsActive cochlear amplificationCochlear efferent systemDistortion product otoacoustic emissionsEfferent systemEfferent pathwaysHearing sensitivityMedial olivocochlear efferent fibersPresynaptic vesicular acetylcholine transportersGap junctionsOlivocochlear efferent fibersHair cellsApplication of acetylcholineCochlear supporting cellsProtection of hearingVesicular acetylcholine transporterActive cochlear amplifierCochlear amplificationPostsynaptic ACh receptorsProduct otoacoustic emissionsMOC efferent systemHair cell activityEfferent nervesEfferent inhibitionEfferent fibersExcess extracellular K+ causes inner hair cell ribbon synapse degeneration
Zhao H, Zhu Y, Liu L. Excess extracellular K+ causes inner hair cell ribbon synapse degeneration. Communications Biology 2021, 4: 24. PMID: 33398038, PMCID: PMC7782724, DOI: 10.1038/s42003-020-01532-w.Peer-Reviewed Original ResearchConceptsCochlear synaptopathySynapse degenerationRibbon synapsesNoise exposureNoise-induced cochlear synaptopathyInner hair cell ribbon synapsesIHC ribbon synapsesGlutamate receptor agonistsBK channel blockersHair cell ribbon synapsesReceptor agonistFirst synapseChannel blockersHearing lossIHC ribbonsHearing disordersDegenerationBK channelsPotential targetSynaptopathyAuditory systemSynapsesExposureSwellingExcitotoxicity
2019
Hearing loss is an early biomarker in APP/PS1 Alzheimer’s disease mice
Liu Y, Fang S, Liu L, Zhu Y, Li C, Chen K, Zhao H. Hearing loss is an early biomarker in APP/PS1 Alzheimer’s disease mice. Neuroscience Letters 2019, 717: 134705. PMID: 31870800, PMCID: PMC7004828, DOI: 10.1016/j.neulet.2019.134705.Peer-Reviewed Original ResearchConceptsAPP/PS1 AD miceDistortion product otoacoustic emissionsAuditory brainstem responseAD miceHearing lossAlzheimer's diseaseDisease miceAPP/PS1 Alzheimer's disease miceAPP/PS1 miceAD mouse modelAlzheimer's disease miceMedial geniculate bodyWild-type littermatesCochlear microphonic recordingsProduct otoacoustic emissionsMonths of ageSpatial learning deficitsPS1 miceUpper brainstemABR thresholdFunction testingGeniculate bodyBrainstem responseLateral lemniscusEarly biomarkers
2018
Knockout of Pannexin-1 Induces Hearing Loss
Chen J, Liang C, Zong L, Zhu Y, Zhao H. Knockout of Pannexin-1 Induces Hearing Loss. International Journal Of Molecular Sciences 2018, 19: 1332. PMID: 29710868, PMCID: PMC5983795, DOI: 10.3390/ijms19051332.Peer-Reviewed Original ResearchConceptsDistortion product otoacoustic emissionsHearing lossKO miceKO mouse lineMouse linesCochlear microphonicsAuditory brainstem response thresholdActive cochlear amplificationPanx1 KO miceAuditory function testsProduct otoacoustic emissionsKnockout mouse lineFunction testsNonsyndromic hearing lossABR thresholdHearing functionHigh incidenceRecent studiesGap junctional proteinReceptor currentsOtoacoustic emissionsMiceCochlear amplificationConsistent phenotypeResponse threshold
2017
A deafness mechanism of digenic Cx26 (GJB2) and Cx30 (GJB6) mutations: Reduction of endocochlear potential by impairment of heterogeneous gap junctional function in the cochlear lateral wall
Mei L, Chen J, Zong L, Zhu Y, Liang C, Jones R, Zhao H. A deafness mechanism of digenic Cx26 (GJB2) and Cx30 (GJB6) mutations: Reduction of endocochlear potential by impairment of heterogeneous gap junctional function in the cochlear lateral wall. Neurobiology Of Disease 2017, 108: 195-203. PMID: 28823936, PMCID: PMC5675824, DOI: 10.1016/j.nbd.2017.08.002.Peer-Reviewed Original ResearchConceptsCochlear lateral wallEndocochlear potentialHearing lossGap junctional functionDeafness mechanismLateral wallHeterozygous miceCx30 mutationsHair cell degenerationHomozygous knockout miceJunctional functionHeterozygous mouse modelGap junctionsOrgan of CortiSame gap junctional plaquesEP reductionFrequent causePathological changesMouse modelKnockout miceReceptor currentsCell degenerationNormal hearingHeterozygous mutationsMiceProgressive age-dependence and frequency difference in the effect of gap junctions on active cochlear amplification and hearing
Zong L, Chen J, Zhu Y, Zhao H. Progressive age-dependence and frequency difference in the effect of gap junctions on active cochlear amplification and hearing. Biochemical And Biophysical Research Communications 2017, 489: 223-227. PMID: 28552523, PMCID: PMC5555358, DOI: 10.1016/j.bbrc.2017.05.137.Peer-Reviewed Original ResearchConceptsActive cochlear amplificationHearing lossCochlear amplificationMice ageGap junctionsAge-related hearing lossSignificant hearing lossPostnatal day 25Cochlear gap junctionsAuditory sensory hair cellsSensory hair cellsNonsyndromic hearing lossHigh incidenceOuter pillar cellsDay 25Deiters' cellsConnexin expressionHair cellsConnexin 26Outer hair cell electromotilityHair cell electromotilityPillar cellsPrevious reportsCochleaAge
2016
Expression and function of pannexins in the inner ear and hearing
Zhao H. Expression and function of pannexins in the inner ear and hearing. BMC Molecular And Cell Biology 2016, 17: 16. PMID: 27229462, PMCID: PMC4896268, DOI: 10.1186/s12860-016-0095-7.Peer-Reviewed Original ResearchConceptsFunction of pannexinsAuditory sensory hair cellsDistinct expression patternsCell apoptotic pathwaysGap junction genesSensory hair cellsGap junction proteinGene familyATP releaseExpression patternsApoptotic pathwayEndocochlear potentialJunction genesPannexinsActive cochlear amplificationPannexin expressionLateral wallCochlear lateral wallJunction proteinsOrgan of CortiHair cellsCritical roleCochlear amplificationIsoformsStria vascularisGap junction mediated miRNA intercellular transfer and gene regulation: A novel mechanism for intercellular genetic communication
Zong L, Zhu Y, Liang R, Zhao H. Gap junction mediated miRNA intercellular transfer and gene regulation: A novel mechanism for intercellular genetic communication. Scientific Reports 2016, 6: 19884. PMID: 26814383, PMCID: PMC4728487, DOI: 10.1038/srep19884.Peer-Reviewed Original ResearchConceptsGenetic communicationGap junction channelsGene regulationGene expressionIntercellular transferJunction channelsSmall regulatory RNAsNovel mechanismSpecific cell typesPassage of ionsRegulatory RNAsCellular processesOrgan developmentConnexin mutationsDifferent miRNAsRecipient cellsMiRNAsCell typesNeighboring cellsCell proliferationConnexin expressionImportant roleMiRNA levelsGap junctionsCell lines
2015
Connexin26 gap junction mediates miRNA intercellular genetic communication in the cochlea and is required for inner ear development
Zhu Y, Zong L, Mei L, Zhao H. Connexin26 gap junction mediates miRNA intercellular genetic communication in the cochlea and is required for inner ear development. Scientific Reports 2015, 5: 15647. PMID: 26490746, PMCID: PMC4614881, DOI: 10.1038/srep15647.Peer-Reviewed Original ResearchConceptsGenetic communicationOrgan developmentInner ear gap junctionsIntercellular communicationGap junctionsCochlear developmentInner ear developmentNon-coding RNAsCx26 knockout miceEar developmentGene expressionIntercellular transferCx26 deficiencyMiR-96 expressionCx30 deficiencyDevelopmental disordersPredominant isoformCell proliferationDeletionCx26Critical roleKnockout miceExpressionMiRNAsMicroRNAsPannexin1 channels dominate ATP release in the cochlea ensuring endocochlear potential and auditory receptor potential generation and hearing
Chen J, Zhu Y, Liang C, Chen J, Zhao H. Pannexin1 channels dominate ATP release in the cochlea ensuring endocochlear potential and auditory receptor potential generation and hearing. Scientific Reports 2015, 5: 10762. PMID: 26035172, PMCID: PMC4451810, DOI: 10.1038/srep10762.Peer-Reviewed Original ResearchConceptsCochlear lateral wallATP releaseHearing lossCochlear microphonicsPotential generationReceptor potentialReceptor potential generationHair cell lossLateral wallNon-junctional channelsEP generationDeficient miceCell lossEndocochlear potentialHair cellsPathological processesCochleaPhysiological conditionsJunction genesGap junction genesConnexin hemichannelsConnexin isoformsHearingDeficiencyReleasePannexin 1 deficiency can induce hearing loss
Zhao H, Zhu Y, Liang C, Chen J. Pannexin 1 deficiency can induce hearing loss. Biochemical And Biophysical Research Communications 2015, 463: 143-147. PMID: 26002464, PMCID: PMC4464954, DOI: 10.1016/j.bbrc.2015.05.049.Peer-Reviewed Original ResearchConceptsDistortion product otoacoustic emissionsHearing lossAuditory brainstem response recordingsProgressive hearing lossProduct otoacoustic emissionsHigh incidenceCell degenerationOtoacoustic emissionsGap junction proteinAcoustic stimulationCell apoptotic pathwaysHair cellsResponse recordingsGene mutationsJunction proteinsExtensive expressionCochleaActive cochlear mechanicsGap junctionsApoptotic pathwayDeficiencyHearingCritical roleCochlear mechanics
2014
Connexin26 (GJB2) deficiency reduces active cochlear amplification leading to late-onset hearing loss
Zhu Y, Chen J, Liang C, Zong L, Chen J, Jones R, Zhao H. Connexin26 (GJB2) deficiency reduces active cochlear amplification leading to late-onset hearing loss. Neuroscience 2014, 284: 719-729. PMID: 25451287, PMCID: PMC4268423, DOI: 10.1016/j.neuroscience.2014.10.061.Peer-Reviewed Original ResearchConceptsLate-onset hearing lossActive cochlear amplificationDistortion product otoacoustic emissionsHearing lossNonsyndromic hearing lossTherapeutic interventionsProgressive hearing lossHair cell lossPostnatal day 5Cochlear amplificationProduct otoacoustic emissionsConditional knockout miceKnockout miceClinical observationsDay 5Cell lossEndocochlear potentialOtoacoustic emissionsNormal hearingCx26 expressionDeafness mechanismMiceCx26 deficiencyCochleaInterventionDeafness induced by Connexin 26 (GJB2) deficiency is not determined by endocochlear potential (EP) reduction but is associated with cochlear developmental disorders
Chen J, Chen J, Zhu Y, Liang C, Zhao H. Deafness induced by Connexin 26 (GJB2) deficiency is not determined by endocochlear potential (EP) reduction but is associated with cochlear developmental disorders. Biochemical And Biophysical Research Communications 2014, 448: 28-32. PMID: 24732355, PMCID: PMC4105360, DOI: 10.1016/j.bbrc.2014.04.016.Peer-Reviewed Original ResearchConceptsAuditory brainstem responseHair cell degenerationKO miceCongenital deafnessEP reductionEndocochlear potentialHearing lossCell degenerationDevelopmental disordersActive cochlear amplificationCx26 knockout miceComplete hearing lossCx26 deficiencyPostnatal day 5Connexin 26 mutationsNonsyndromic hearing lossBrainstem responseMouse modelKnockout miceDay 5Deafness mechanismMajor causeMiceDeafnessDisordersThe role of an inwardly rectifying K+ channel (Kir4.1) in the inner ear and hearing loss
Chen J, Zhao H. The role of an inwardly rectifying K+ channel (Kir4.1) in the inner ear and hearing loss. Neuroscience 2014, 265: 137-146. PMID: 24480364, PMCID: PMC4007161, DOI: 10.1016/j.neuroscience.2014.01.036.Peer-Reviewed Original ResearchConceptsInner earGanglion neuronsHearing lossSpiral ganglion neuron degenerationPotassium channelsSatellite glial cellsSpiral ganglion neuronsKir4.1 potassium channelsPathogenesis of deafnessPotassium channel functionNeuron degenerationSeSAME syndromeFunctional impairmentGlial cellsCochlear ganglionTherapeutic strategiesKir4.1 channelsCochlear developmentStria vascularisKir4.1 subunitKir4.1Scala mediaIntermediate cellsAbsence of EpEar
2013
Active cochlear amplification is dependent on supporting cell gap junctions
Zhu Y, Liang C, Chen J, Zong L, Chen G, Zhao H. Active cochlear amplification is dependent on supporting cell gap junctions. Nature Communications 2013, 4: 1786. PMID: 23653198, PMCID: PMC3675877, DOI: 10.1038/ncomms2806.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAuditory ThresholdCochlear Microphonic PotentialsConnexin 26ConnexinsEvoked Potentials, Auditory, Brain StemGap JunctionsGene DeletionGene TargetingHair Cells, Auditory, OuterHearing LossLabyrinth Supporting CellsMiceMice, KnockoutMolecular Motor ProteinsNonlinear DynamicsOtoacoustic Emissions, SpontaneousSpiral GanglionConceptsActive cochlear amplificationOuter hair cellsCell gap junctionsHearing lossCochlear amplificationHair cellsGap junctionsDistortion product otoacoustic emissionsOuter hair cell electromotilityHair cell electromotilitySevere hearing lossProduct otoacoustic emissionsShorter outer hair cellsHair-bundle movementsOuter pillar cellsLeftward shiftOtoacoustic emissionsAcoustic stimulationDeiters' cellsHearing sensitivityConnexin 26Active cochlear mechanicsNovel findingsPillar cellsBundle movementMutation of the ATP-gated P2X2 receptor leads to progressive hearing loss and increased susceptibility to noise
Yan D, Zhu Y, Walsh T, Xie D, Yuan H, Sirmaci A, Fujikawa T, Wong A, Loh T, Du L, Grati M, Vlajkovic S, Blanton S, Ryan A, Chen Z, Thorne P, Kachar B, Tekin M, Zhao H, Housley G, King M, Liu X. Mutation of the ATP-gated P2X2 receptor leads to progressive hearing loss and increased susceptibility to noise. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 2228-2233. PMID: 23345450, PMCID: PMC3568371, DOI: 10.1073/pnas.1222285110.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAmino Acid SequenceAnimalsDisease Models, AnimalEvoked Potentials, AuditoryFemaleGenes, DominantHearing Loss, Noise-InducedHearing Loss, SensorineuralHeterozygoteHumansIon Channel GatingMaleMiceMice, Inbred C57BLMice, KnockoutMolecular Sequence DataMutation, MissensePedigreePenetranceReceptors, Purinergic P2X2Sequence Homology, Amino AcidYoung AdultConceptsHigh-frequency hearing lossHearing lossNoise-induced hearing lossAge-related hearing lossProgressive hearing lossSevere progressive hearing lossCoexpression of mutantLoss of ATPLoss of functionNoise exposureNormal hearingReceptor subunitsHuman morbidityP2X2 receptorsMajor causeYoung adultsYoung adulthoodEarly exposureHallmark featureFamily membersReceptorsExposureIndex familyShared causeCause
2012
Cell degeneration is not a primary causer for Connexin26 (GJB2) deficiency associated hearing loss
Liang C, Zhu Y, Zong L, Lu G, Zhao H. Cell degeneration is not a primary causer for Connexin26 (GJB2) deficiency associated hearing loss. Neuroscience Letters 2012, 528: 36-41. PMID: 22975134, PMCID: PMC3467974, DOI: 10.1016/j.neulet.2012.08.085.Peer-Reviewed Original ResearchConceptsHair cell lossAuditory brainstem responseCell degenerationCell lossNeuron degenerationPostnatal developmentCx26 deficiencyCochlear hair cell lossSpiral ganglion neuron degenerationDevelopment disordersCx26 knockout miceHair cellsHair cell functionOuter hair cellsSG neuronsNonsyndromic hearing lossKO miceBrainstem responseCochlear cellsHearing lossBasal turnMouse modelKnockout miceCongenital deafnessSignificant degenerationATP activates P2X receptors to mediate gap junctional coupling in the cochlea
Zhu Y, Zhao H. ATP activates P2X receptors to mediate gap junctional coupling in the cochlea. Biochemical And Biophysical Research Communications 2012, 426: 528-532. PMID: 22982314, PMCID: PMC3471361, DOI: 10.1016/j.bbrc.2012.08.119.Peer-Reviewed Original ResearchConceptsP2X receptorsGap junctional couplingCochlear gap junctionsP2Y receptor agonist UTPGap junctionsJunctional couplingP2X receptor antagonistMetabotropic purinergic receptorsReceptor agonist UTPStimulation of ATPPhysiological levelsReceptor antagonistP2Y receptorsPurinergic controlPurinergic receptorsBenzoylbenzoyl-ATPNoise stressReceptorsIonic homeostasisCochleaDisulfonic acidCritical roleIntercellular channelsATPCells
2011
Pannexin channels are not gap junction hemichannels
Sosinsky G, Boassa D, Dermietzel R, Duffy H, Laird D, MacVicar B, Naus C, Penuela S, Scemes E, Spray D, Thompson R, Zhao H, Dahl G. Pannexin channels are not gap junction hemichannels. Channels 2011, 5: 193-197. PMID: 21532340, PMCID: PMC3704572, DOI: 10.4161/chan.5.3.15765.Peer-Reviewed Original Research