2023
The biology of hearing and hearing loss: New insights from naked mole-rats into mechanisms and adaptive responses
Pyott S, Jagersma J, van Tuinen M, Koch U, Lauer A, Park T, Lysakowski A, Santos-Sacchi J, Kumar S, Ryugo D. The biology of hearing and hearing loss: New insights from naked mole-rats into mechanisms and adaptive responses. The Journal Of The Acoustical Society Of America 2023, 154: a298-a299. DOI: 10.1121/10.0023589.Peer-Reviewed Original ResearchBiology of hearingBundle proteinHair bundle proteinAdaptive responseAmino acid substitutionsEusocial lifestyleEvolutionary legacySubterranean speciesPositive selectionComparative organizationAcid substitutionsHair bundlesCochlear amplificationBiologySpeciesProteinNew insightsHearing lossPoor hearingComparative approachDisease modelsMechanistic approachCentral auditory structuresCentral compensationRats resultsPharmacological Modulation of Energy and Metabolic Pathways Protects Hearing in the Fus1/Tusc2 Knockout Model of Mitochondrial Dysfunction and Oxidative Stress
Tan W, Santos-Sacchi J, Tonello J, Shanker A, Ivanova A. Pharmacological Modulation of Energy and Metabolic Pathways Protects Hearing in the Fus1/Tusc2 Knockout Model of Mitochondrial Dysfunction and Oxidative Stress. Antioxidants 2023, 12: 1225. PMID: 37371955, PMCID: PMC10294946, DOI: 10.3390/antiox12061225.Peer-Reviewed Original ResearchPharmacological modulationKO miceMitochondrial metabolismComparative gene expression analysisMetabolic pathwaysOxidative stressCritical biological processesHearing-related genesDrug-specific responsesPremature hearing lossGene expression analysisAdrenal axisHearing lossImmune responseMitochondrial morphologyMotor proteinsExpression analysisVoltage-gated channelsBiological processesMTOR pathwayNormal hearingPronounced upregulationMolecular pathwaysMitochondrial activityEnergy sensingMegahertz Sampling of Prestin (SLC26a5) Voltage-Sensor Charge Movements in Outer Hair Cell Membranes Reveals Ultrasonic Activity that May Support Electromotility and Cochlear Amplification
Santos-Sacchi J, Bai J, Navaratnam D. Megahertz Sampling of Prestin (SLC26a5) Voltage-Sensor Charge Movements in Outer Hair Cell Membranes Reveals Ultrasonic Activity that May Support Electromotility and Cochlear Amplification. Journal Of Neuroscience 2023, 43: 2460-2468. PMID: 36868859, PMCID: PMC10082455, DOI: 10.1523/jneurosci.2033-22.2023.Peer-Reviewed Original ResearchConceptsConformational switchingMammalian hearingMembrane motor proteinCochlear amplificationMotor protein prestinVoltage-sensor charge movementOuter hair cell electromotilityHair cell electromotilityProtein prestinMotor proteinsConformation switchingCharge movementPrestinPrestin activityCell membraneOHC electromotilityHair cell membraneElectromotilityTransmembrane voltageOrgan of CortiAmplificationMammalsMembrane capacitanceProtein
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 wavesNeuronsOn the frequency response of prestin charge movement in membrane patches
Santos-Sacchi J, Tan W. On the frequency response of prestin charge movement in membrane patches. Biophysical Journal 2022, 121: 2371-2379. PMID: 35598044, PMCID: PMC9279172, DOI: 10.1016/j.bpj.2022.05.020.Peer-Reviewed Original ResearchPhysiology and biophysics of outer hair cells: The cells of Dallos
Santos-Sacchi J, Navaratnam D. Physiology and biophysics of outer hair cells: The cells of Dallos. Hearing Research 2022, 423: 108525. PMID: 35599199, DOI: 10.1016/j.heares.2022.108525.Peer-Reviewed Original ResearchSingle particle cryo-EM structure of the outer hair cell motor protein prestin
Butan C, Song Q, Bai JP, Tan WJT, Navaratnam D, Santos-Sacchi J. Single particle cryo-EM structure of the outer hair cell motor protein prestin. Nature Communications 2022, 13: 290. PMID: 35022426, PMCID: PMC8755724, DOI: 10.1038/s41467-021-27915-z.Peer-Reviewed Original ResearchConceptsTransmembrane domainProtein prestinSingle-particle cryo-EM structuresAnti-sigma factor antagonist domainOuter hair cell motor protein prestinCryo-EM structureCryo-electron microscopyMotor protein prestinSLC26 family membersSulfate transportersTransmembrane segmentsPrestin functionÅ resolutionPrestinOHC electromotilityOpen stateCochlear amplificationPutative mechanismsFamily membersDomainRepeatsSLC26A9TransportersMutationsElectromotility
2021
Coupling between outer hair cell electromotility and prestin sensor charge depends on voltage operating point
Santos-Sacchi J, Tan WJT. Coupling between outer hair cell electromotility and prestin sensor charge depends on voltage operating point. Hearing Research 2021, 423: 108373. PMID: 34776274, PMCID: PMC9054947, DOI: 10.1016/j.heares.2021.108373.Peer-Reviewed Original ResearchConceptsOperating voltage rangeFrequency responseAC voltage excitationSlow frequency responseVoltage operating pointNonlinear capacitanceOperating voltageOperating pointVoltage excitationVoltage rangeSpecial Issue Outer hair cellJoseph Santos-SacchiVoltageKumar NavaratnamLoadVoltage-sensor charge movementGenes 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 overlapExpressionThe naked truth: a comprehensive clarification and classification of current ‘myths’ in naked mole‐rat biology
Buffenstein R, Amoroso V, Andziak B, Avdieiev S, Azpurua J, Barker AJ, Bennett NC, Brieño‐Enríquez M, Bronner GN, Coen C, Delaney MA, Dengler‐Crish C, Edrey YH, Faulkes CG, Frankel D, Friedlander G, Gibney PA, Gorbunova V, Hine C, Holmes MM, Jarvis JUM, Kawamura Y, Kutsukake N, Kenyon C, Khaled WT, Kikusui T, Kissil J, Lagestee S, Larson J, Lauer A, Lavrenchenko LA, Lee A, Levitt JB, Lewin GR, Hardell K, Lin TD, Mason MJ, McCloskey D, McMahon M, Miura K, Mogi K, Narayan V, O'Connor TP, Okanoya K, O'Riain MJ, Park TJ, Place NJ, Podshivalova K, Pamenter ME, Pyott SJ, Reznick J, Ruby JG, Salmon AB, Santos‐Sacchi J, Sarko DK, Seluanov A, Shepard A, Smith M, Storey KB, Tian X, Vice EN, Viltard M, Watarai A, Wywial E, Yamakawa M, Zemlemerova ED, Zions M, St. John Smith E. The naked truth: a comprehensive clarification and classification of current ‘myths’ in naked mole‐rat biology. Biological Reviews 2021, 97: 115-140. PMID: 34476892, PMCID: PMC9277573, DOI: 10.1111/brv.12791.Peer-Reviewed Original ResearchState dependent effects on the frequency response of prestin’s real and imaginary components of nonlinear capacitance
Santos-Sacchi J, Navaratnam D, Tan WJT. State dependent effects on the frequency response of prestin’s real and imaginary components of nonlinear capacitance. Scientific Reports 2021, 11: 16149. PMID: 34373481, PMCID: PMC8352928, DOI: 10.1038/s41598-021-95121-4.Peer-Reviewed Original ResearchEfferent feedback controls bilateral auditory spontaneous activity
Wang Y, Sanghvi M, Gribizis A, Zhang Y, Song L, Morley B, Barson DG, Santos-Sacchi J, Navaratnam D, Crair M. Efferent feedback controls bilateral auditory spontaneous activity. Nature Communications 2021, 12: 2449. PMID: 33907194, PMCID: PMC8079389, DOI: 10.1038/s41467-021-22796-8.Peer-Reviewed Original ResearchConceptsSpontaneous activityEfferent modulationEfferent pathwaysMedial olivocochlear systemCentral nervous systemCentral auditory systemInner hair cellsAuditory systemNicotinic acetylcholine receptorsSpontaneous activity patternsOlivocochlear systemHearing onsetEfferent systemChemogenetic experimentsBilateral couplingNervous systemAcetylcholine receptorsCircuit formationEfferent feedbackFiring patternsHair cellsΑ9/Auditory sensitivityBilateral correlationActivity patternsAnimal Models for Otolaryngological Disorders
Doukas S, Bartoshuk L, Manes R, Michaelides E, Santos-Sacchi J, Spock T, Sukys J, Sasaki C. Animal Models for Otolaryngological Disorders. 2021, 775-796. DOI: 10.1201/9780429439964-34.Peer-Reviewed Original ResearchComprehensive somatosensory and neurological phenotyping of NCS1 knockout mice
Nguyen LD, Nolte LG, Tan WJT, Giuvelis D, Santos-Sacchi J, Bilsky E, Ehrlich BE. Comprehensive somatosensory and neurological phenotyping of NCS1 knockout mice. Scientific Reports 2021, 11: 2372. PMID: 33504822, PMCID: PMC7840744, DOI: 10.1038/s41598-021-81650-5.Peer-Reviewed Original ResearchConceptsNeuronal calcium sensor-1Peripheral nervous systemNervous systemMale miceKnockout micePaclitaxel-induced peripheral neuropathyKO modelKO male miceNCS1 expressionMammalian nervous systemPrecise physiological significanceSex-specific effectsPeripheral neuropathyFemale miceModulatory roleBehavioral testsPharmacological targetsMiceNeurodegenerative diseasesClinical interestMemory acquisitionMotor performancePathological statesAffective behaviorDisease
2020
Functional, Morphological, and Evolutionary Characterization of Hearing in Subterranean, Eusocial African Mole-Rats
Pyott SJ, van Tuinen M, Screven LA, Schrode KM, Bai JP, Barone CM, Price SD, Lysakowski A, Sanderford M, Kumar S, Santos-Sacchi J, Lauer AM, Park TJ. Functional, Morphological, and Evolutionary Characterization of Hearing in Subterranean, Eusocial African Mole-Rats. Current Biology 2020, 30: 4329-4341.e4. PMID: 32888484, PMCID: PMC8109146, DOI: 10.1016/j.cub.2020.08.035.Peer-Reviewed Original ResearchConceptsHair bundle morphologyAmino acid substitutionsAltered hearingLink proteinAcid substitutionsUnique evolutionary trajectoryMolecular evolutionary analysisCochlear amplificationEvolutionary characterizationEvolutionary analysisHuman hearing lossEvolutionary trajectoriesBundle morphologyPrestin functionAfrican Mole-RatsCodon levelSelection pressureSubterranean lifestyleSubterranean rodentsMole-RatUnique lifestyleProteinHair cellsSpeciesOuter hair cellsAuthor Correction: Prestin kinetics and corresponding frequency dependence augment during early development of the outer hair cell within the mouse organ of Corti
Bai JP, Navaratnam D, Santos-Sacchi J. Author Correction: Prestin kinetics and corresponding frequency dependence augment during early development of the outer hair cell within the mouse organ of Corti. Scientific Reports 2020, 10: 14401. PMID: 32848168, PMCID: PMC7449959, DOI: 10.1038/s41598-020-70538-5.Peer-Reviewed Original ResearchCalcium‐induced calcium release in proximity to hair cell BK channels revealed by PKA activation
Bai J, Xue N, Lawal O, Nyati A, Santos‐Sacchi J, Navaratnam D. Calcium‐induced calcium release in proximity to hair cell BK channels revealed by PKA activation. Physiological Reports 2020, 8: e14449. PMID: 32748549, PMCID: PMC7399380, DOI: 10.14814/phy2.14449.Peer-Reviewed Original ResearchConceptsBK channelsBK currentsCalcium-activated potassium channelsLarge-conductance calcium-activated potassium channelsCalcium-induced calcium releaseEntry of CaSlo subunitSynaptic releaseCalcium releaseChicken hair cellsPotassium channelsHair cellsIP3 receptorCICRA ActivationPKA activationActivationCritical roleImagingReleaseRyanodineComplex nonlinear capacitance in outer hair cell macro-patches: effects of membrane tension
Santos-Sacchi J, Tan W. Complex nonlinear capacitance in outer hair cell macro-patches: effects of membrane tension. Scientific Reports 2020, 10: 6222. PMID: 32277153, PMCID: PMC7148382, DOI: 10.1038/s41598-020-63201-6.Peer-Reviewed Original ResearchMaturation 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
Cytomegalovirus infects the developing Organ of Corti in a mouse model of virally induced deafness
Ornaghi S, Bai J, Santos-Sacchi J, Navaratnam D, Vergani P, van den Pol A, Paidas M. Cytomegalovirus infects the developing Organ of Corti in a mouse model of virally induced deafness. American Journal Of Obstetrics And Gynecology 2019, 221: 695-696. DOI: 10.1016/j.ajog.2019.10.063.Peer-Reviewed Original Research