Featured Publications
Differential outcomes of high‐fat diet on age‐related rescaling of cochlear frequency place coding
Zhang Y, Lin G, Xue N, Wang Y, Du T, Liu H, Xiong W, Shang W, Wu H, Song L. Differential outcomes of high‐fat diet on age‐related rescaling of cochlear frequency place coding. The FASEB Journal 2023, 37: e23167. PMID: 37651093, DOI: 10.1096/fj.202300457rr.Peer-Reviewed Original ResearchConceptsAge-related hearing lossHigh-fat dietHearing lossEffects of HFDLoss of OHCsActivation of TRPV1Sensorineural hearing lossCBA/CaJPlace codingCochlear frequency selectivityTRPV1 expressionOHC functionInflammatory responseCommon causeHFD cohortGenetic backgroundYounger ageArachidonic acidCochlear lengthHair cellsPrestin levelsLipid homeostasisRescuing effectCochlear amplificationAgePrestin derived OHC surface area reduction underlies age‐related rescaling of frequency place coding
Zhang Y, Lin G, Wang Y, Xue N, Lin X, Du T, Xiong W, Song L. Prestin derived OHC surface area reduction underlies age‐related rescaling of frequency place coding. Hearing Research 2021, 423: 108406. PMID: 34933788, DOI: 10.1016/j.heares.2021.108406.Peer-Reviewed Original Research
2024
The p. S178L mutation in Tbc1d24 disrupts endosome‐mediated synaptic vesicle trafficking of cochlear hair cells and leads to hearing impairment in mice
Chen P, Hou S, Li G, Lin Y, Lu J, Song L, Li G, Pang X, Wu H, Yang T. The p. S178L mutation in Tbc1d24 disrupts endosome‐mediated synaptic vesicle trafficking of cochlear hair cells and leads to hearing impairment in mice. Clinical Genetics 2024 PMID: 39400345, DOI: 10.1111/cge.14620.Peer-Reviewed Original ResearchNon-syndromic hearing lossSynaptic vesiclesRibbon synapses of cochlear inner hair cellsAutosomal dominant non-syndromic hearing lossDominant non-syndromic hearing lossEndosome-like vacuolesEndosomal membrane traffickingInner hair cellsSynaptic vesicle traffickingHearing lossRibbon synapsesHair cell ribbon synapsesKnock-in mouse modelMutant miceSustained exocytosisVesicle traffickingEndosomal traffickingMembrane traffickingVesicle recyclingIn vitro interactionCochlear inner hair cellsReduced exocytosisWave I amplitudeMild hearing lossAuditory brainstem responseDMXL2 Is Required for Endocytosis and Recycling of Synaptic Vesicles in Auditory Hair Cells
Peng H, Wang L, Gao Y, Liu H, Lin G, Kong Y, Xu P, Liu H, Yuan Q, Liu H, Song L, Yang T, Wu H. DMXL2 Is Required for Endocytosis and Recycling of Synaptic Vesicles in Auditory Hair Cells. Journal Of Neuroscience 2024, 44: e1405232024. PMID: 39147590, PMCID: PMC11411588, DOI: 10.1523/jneurosci.1405-23.2024.Peer-Reviewed Original ResearchEndocytic membrane retrievalSynaptic vesiclesSynaptic exocytosisMembrane retrievalEndocytic compartmentsMolecular machineryRecycling of synaptic vesiclesReserve poolMembrane capacitance measurementsRibbon synapses of inner hair cellsElectron microscopy reconstructionsAuditory synaptopathyMutant miceSynaptic endocytosisCell-specific knockout miceHuman homologMembrane-proximalHair cellsAuditory hair cellsMolecular basisEndocytosisRibbon synapsesInner hair cellsHearing lossDMXL2Revisiting the Potency of Tbx2 Expression in Transforming Outer Hair Cells into Inner Hair Cells at Multiple Ages In Vivo
Bi Z, Ren M, Zhang Y, He S, Song L, Li X, Liu Z. Revisiting the Potency of Tbx2 Expression in Transforming Outer Hair Cells into Inner Hair Cells at Multiple Ages In Vivo. Journal Of Neuroscience 2024, 44: e1751232024. PMID: 38688721, PMCID: PMC11154855, DOI: 10.1523/jneurosci.1751-23.2024.Peer-Reviewed Original Research
2023
In situ regeneration of inner hair cells in the damaged cochlea by temporally regulated co-expression of Atoh1 and Tbx2
Li X, Ren M, Gu Y, Zhu T, Zhang Y, Li J, Li C, Wang G, Song L, Bi Z, Liu Z. In situ regeneration of inner hair cells in the damaged cochlea by temporally regulated co-expression of Atoh1 and Tbx2. Development 2023, 150 PMID: 38078650, DOI: 10.1242/dev.201888.Peer-Reviewed Original ResearchDifferential regulation of hair cell actin cytoskeleton mediated by SRF and MRTFB
Zhou L, Jin C, Wang W, Song L, Shin J, Du T, Wu H. Differential regulation of hair cell actin cytoskeleton mediated by SRF and MRTFB. ELife 2023, 12: e90155. PMID: 37982489, PMCID: PMC10703445, DOI: 10.7554/elife.90155.Peer-Reviewed Original ResearchConceptsActin cytoskeletonRegulation of actin cytoskeletonMRTF-SRF pathwayModulating actin dynamicsCell actin cytoskeletonCuticular plateActin cytoskeleton organizationActin cytoskeleton activityTranscriptional regulation mechanismRNA-seq analysisF-actin intensityHair cell developmentProfiles of genesActin dynamicsCytoskeleton organizationTranscriptional regulationF-actinCalponin 2Cytoskeleton activityHair bundle morphologyTranscriptome analysisDifferential regulationCell developmentCell-specific deletionCytoskeletonCochlear transcript diversity and its role in auditory functions implied by an otoferlin short isoform
Liu H, Liu H, Wang L, Song L, Jiang G, Lu Q, Yang T, Peng H, Cai R, Zhao X, Zhao T, Wu H. Cochlear transcript diversity and its role in auditory functions implied by an otoferlin short isoform. Nature Communications 2023, 14: 3085. PMID: 37248244, PMCID: PMC10227054, DOI: 10.1038/s41467-023-38621-3.Peer-Reviewed Original ResearchConceptsShort isoformEndocytic membrane retrievalRNA sequencing techniquesDiverse biological functionsInner hair cellsTranscript diversityUnannotated transcriptsRNA-seqAlternative isoformsMembrane retrievalBiological functionsGENCODE databasesKey proteinsIsoform resolutionSequencing techniquesSustained exocytosisIsoformsMechanistic understandingAuditory functionSanger sequencingHair cellsTranscriptsRT-PCRSynaptic transmissionAuditory phenotypeRole of mitochondrial dysfunction and oxidative stress in sensorineural hearing loss
Tan W, Song L. Role of mitochondrial dysfunction and oxidative stress in sensorineural hearing loss. Hearing Research 2023, 434: 108783. PMID: 37167889, DOI: 10.1016/j.heares.2023.108783.Peer-Reviewed Original ResearchConceptsSensorineural hearing lossOtotoxic drugsMitochondrial dysfunctionReactive oxygen speciesOxidative stressHearing lossDevelopment of SNHLMitochondrial reactive oxygen speciesSpiral ganglion neuronsMitochondrial DNA mutationsPrecise pathophysiological mechanismsSensory hair cellsHair cell mitochondriaConsequent oxidative stressCentral etiological roleMtDNA mutationsPathophysiological mechanismsGanglion neuronsAntioxidant therapyCalcium dysregulationDNA mutationsCell mitochondriaClinical studiesCochlear cellsEtiological role
2022
Outer hair cell function is normal in βV spectrin knockout mice
Stankewich MC, Bai JP, Stabach PR, Khan S, Tan WJT, Surguchev A, Song L, Morrow JS, Santos-Sacchi J, Navaratnam DS. Outer hair cell function is normal in βV spectrin knockout mice. Hearing Research 2022, 423: 108564. PMID: 35864018, DOI: 10.1016/j.heares.2022.108564.Peer-Reviewed Original ResearchConceptsOuter hair cellsAuditory brainstem response wavesAuditory thresholdOuter hair cell functionSpiral ganglion neuronsEfferent nerve fibersHair cell functionNumber of afferentsGanglion neuronsNerve fibersKnockout miceNeuronal structuresMiceHair cellsCell functionElectromechanical activityPutative roleType IOngoing investigationExon deletionsSynaptopathyAfferentsData supportResponse wavesNeuronsPrestin-Mediated Frequency Selectivity Does not Cover Ultrahigh Frequencies in Mice
Li J, Liu S, Song C, Zhu T, Zhao Z, Sun W, Wang Y, Song L, Xiong W. Prestin-Mediated Frequency Selectivity Does not Cover Ultrahigh Frequencies in Mice. Neuroscience Bulletin 2022, 38: 769-784. PMID: 35279808, PMCID: PMC9276951, DOI: 10.1007/s12264-022-00839-4.Peer-Reviewed Original ResearchConceptsOuter hair cellsCation channel blockerCochlear outer hair cellsPrestin knockout miceAudiometric measurementsChannel blockersPharmacogenetic manipulationCochlear sensitivityMiceSpecific ablationHair cellsTarget cellsBehavior testsHearingMembrane potentialLow-pass featureAblationUltrasonic hearingCellsPrestinBlockersMembrane resonanceIn vivo CRISPR‐Cas9‐mediated DNA chop identifies a cochlear outer hair cell‐specific enhancer
Sun Y, Zhang Y, Zhang D, Wang G, Song L, Liu Z. In vivo CRISPR‐Cas9‐mediated DNA chop identifies a cochlear outer hair cell‐specific enhancer. The FASEB Journal 2022, 36: e22233. PMID: 35225354, DOI: 10.1096/fj.202100421rr.Peer-Reviewed Original ResearchConceptsDNA fragment deletionKbp fragmentKbp segmentFragment deletionCell-specific enhancerOuter hair cellsLarge DNA fragment deletionGreen fluorescent proteinCRISPR/Motor proteinsIntron regionsGene therapeutic applicationsFluorescent proteinDifferent speciesCochlear outer hair cellsBp fragmentEnhancerSLC26A5Hair cellsEGFPProteinTransgenic miceDeletionKbpPrestin expression
2021
Real-time threshold determination of auditory brainstem responses by cross-correlation analysis
Wang H, Li B, Lu Y, Han K, Sheng H, Zhou J, Qi Y, Wang X, Huang Z, Song L, Hua Y. Real-time threshold determination of auditory brainstem responses by cross-correlation analysis. IScience 2021, 24: 103285. PMID: 34765914, PMCID: PMC8571499, DOI: 10.1016/j.isci.2021.103285.Peer-Reviewed Original ResearchGenes related to SNPs identified by Genome-wide association studies of age-related hearing loss show restriction to specific cell types in the adult mouse cochlea
Xue N, Song L, Song Q, Santos-Sacchi J, Wu H, Navaratnam D. Genes related to SNPs identified by Genome-wide association studies of age-related hearing loss show restriction to specific cell types in the adult mouse cochlea. Hearing Research 2021, 410: 108347. PMID: 34536825, DOI: 10.1016/j.heares.2021.108347.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingApical cell polarityGenome-wide association studiesAdult mouse cochleaSpecific cell typesCell polaritySubtypes of cellsSignificant genetic componentSingle nucleotide polymorphismsVesicle recyclingRNA sequencingAssociation studiesGenesVarying ExpressionCell typesGenetic componentNucleotide polymorphismsSNPsMouse cochleaCell functionGenesetsHair cellsHair cell functionSignificant overlapExpression
2020
Down-regulation of AMPK signaling pathway rescues hearing loss in TFB1 transgenic mice and delays age-related hearing loss
Zhao J, Li G, Zhao X, Lin X, Gao Y, Raimundo N, Li G, Shang W, Wu H, Song L. Down-regulation of AMPK signaling pathway rescues hearing loss in TFB1 transgenic mice and delays age-related hearing loss. Aging 2020, 12: 5590-5611. PMID: 32240104, PMCID: PMC7185105, DOI: 10.18632/aging.102977.Peer-Reviewed Original ResearchConceptsReactive oxygen speciesPro-survival functionRole of AMPKRegulation of AMPKActivation of AMPKAnti-apoptotic signalingPro-apoptotic signalingProtein kinaseOuter hair cellsAMPK activationAMPK hyperactivationROS-AMPKSpiral ganglion neuronsAMPK downregulationApoptosis pathwayHair cell synapsesAMPKMitochondrial dysfunctionCochlear tissuesCell growthRedox imbalanceBcl2 pathwayInner hair cell synapsesOxygen speciesHair cellsMaturation of Voltage-induced Shifts in SLC26a5 (Prestin) Operating Point during Trafficking and Membrane Insertion
Zhai F, Song L, Bai JP, Dai C, Navaratnam D, Santos-Sacchi J. Maturation of Voltage-induced Shifts in SLC26a5 (Prestin) Operating Point during Trafficking and Membrane Insertion. Neuroscience 2020, 431: 128-133. PMID: 32061780, PMCID: PMC8720582, DOI: 10.1016/j.neuroscience.2020.02.003.Peer-Reviewed Original ResearchConceptsMembrane motor proteinVoltage-dependent proteinsMembrane insertionOuter hair cellsMotor proteinsPrestin densityHEK cell linesConformational changesBiophysical forcesOHC electromotilityProteinCell linesMembrane potentialCooperative interactionsPrestinHair cellsCochlear amplificationTransmembrane voltageNonlinear capacitanceMammalsTraffickingVoltage-induced shiftElectromotilityMaturationMembrane
2019
Hearing consequences in Gjb2 knock-in mice: implications for human p.V37I mutation
Lin X, Li G, Zhang Y, Zhao J, Lu J, Gao Y, Liu H, Li G, Yang T, Song L, Wu H. Hearing consequences in Gjb2 knock-in mice: implications for human p.V37I mutation. Aging 2019, 11: 7416-7441. PMID: 31562289, PMCID: PMC6782001, DOI: 10.18632/aging.102246.Peer-Reviewed Original ResearchConceptsHomozygous miceLate-onset progressive hearing lossV37I mutationABR wave I latencySpiral ganglion neuron lossOuter hair cell functionSignificant hair cell lossMiddle ear injectionStria vascularis atrophyWave I latencyABR threshold elevationsProgressive hearing lossHair cell lossHair cell functionEnvironmental insultsI latencyNeuron lossCochlear pathologyHearing lossEar injectionMouse modelCell lossNoise exposureSystemic applicationThreshold elevationFunctional alteration of ribbon synapses in inner hair cells by noise exposure causing hidden hearing loss
Liu H, Lu J, Wang Z, Song L, Wang X, Li G, Wu H. Functional alteration of ribbon synapses in inner hair cells by noise exposure causing hidden hearing loss. Neuroscience Letters 2019, 707: 134268. PMID: 31103727, DOI: 10.1016/j.neulet.2019.05.022.Peer-Reviewed Original ResearchConceptsInner hair cellsModerate noise exposureHearing lossRibbon synapsesNoise exposureHair cellsPersistent reductionWhole-cell patch-clamp recordingsNoise-induced hearing lossSynapse functionAuditory afferent fibersHidden hearing lossABR wave ISynaptic vesiclesAuditory brainstem response (ABR) amplitudesPatch-clamp recordingsSevere noise exposureWhole mount immunofluorescence stainingPatch-clamp electrophysiologySensory hair cellsAfferent fibersABR thresholdPersistent alterationsExposure altersFunctional alterationsModulators of Kv3 Potassium Channels Rescue the Auditory Function of Fragile X Mice
El-Hassar L, Song L, Tan WJT, Large CH, Alvaro G, Santos-Sacchi J, Kaczmarek LK. Modulators of Kv3 Potassium Channels Rescue the Auditory Function of Fragile X Mice. Journal Of Neuroscience 2019, 39: 4797-4813. PMID: 30936239, PMCID: PMC6561694, DOI: 10.1523/jneurosci.0839-18.2019.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAuditory PathwaysAuditory PerceptionBrain StemCochlear NucleusElectrophysiological PhenomenaEvoked Potentials, Auditory, Brain StemFemaleFragile X Mental Retardation ProteinFragile X SyndromeHydantoinsIn Vitro TechniquesMaleMiceMice, KnockoutPatch-Clamp TechniquesPyridinesShaw Potassium ChannelsConceptsAuditory brainstem responseWild-type animalsRepetitive firingABR wave ICurrent-clamp recordingsAuditory brainstem nucleiVoltage-clamp recordingsHigh-frequency firingSingle action potentialFragile X syndromeTrapezoid bodyBrainstem nucleiBrainstem responseMedial nucleusAuditory brainstemAuditory nerveWave IWave IVAction potentialsSensory stimuliKv3.1 channelsCentral processingMental retardation proteinHigh sound levelsMiceCellular Differences in the Cochlea of CBA and B6 Mice May Underlie Their Difference in Susceptibility to Hearing Loss
Liu H, Li G, Lu J, Gao Y, Song L, Li G, Wu H. Cellular Differences in the Cochlea of CBA and B6 Mice May Underlie Their Difference in Susceptibility to Hearing Loss. Frontiers In Cellular Neuroscience 2019, 13: 60. PMID: 30873008, PMCID: PMC6400987, DOI: 10.3389/fncel.2019.00060.Peer-Reviewed Original ResearchInner hair cellsEarly-onset hearing lossB6 miceOnset hearing lossHearing lossRibbon synapsesOuter hair cell functionMouse strainsCBA/CaJ miceWave I latencySpiral ganglion neuronsSynaptic vesiclesHair cell functionCellular differencesStable hearingSimilar hearing thresholdsI latencyABR thresholdGanglion neuronsGlutamate toxicityHearing thresholdsWave IMiceHair cellsCell function