{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T01:28:17Z","timestamp":1787621297597,"version":"build-2736575974"},"reference-count":87,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T00:00:00Z","timestamp":1636588800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["R01DC013817"],"award-info":[{"award-number":["R01DC013817"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["R01DC000088"],"award-info":[{"award-number":["R01DC000088"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["R01DC014712"],"award-info":[{"award-number":["R01DC014712"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"United States Department of Defense","doi-asserted-by":"publisher","award":["MR130240"],"award-info":[{"award-number":["MR130240"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"United States Department of Defense","doi-asserted-by":"publisher","award":["W81XWH2110578"],"award-info":[{"award-number":["W81XWH2110578"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Recent studies have identified sex-differences in auditory physiology and in the susceptibility to noise-induced hearing loss (NIHL). We hypothesize that 17\u03b2-estradiol (E2), a known modulator of auditory physiology, may underpin sex-differences in the response to noise trauma. Here, we gonadectomized B6CBAF1\/J mice and used a combination of electrophysiological and histological techniques to study the effects of estrogen replacement on peripheral auditory physiology in the absence of noise exposure and on protection from NIHL. Functional analysis of auditory physiology in gonadectomized female mice revealed that E2-treatment modulated the peripheral response to sound in the absence of changes to the endocochlear potential compared to vehicle-treatment. E2-replacement in gonadectomized female mice protected against hearing loss following permanent threshold shift (PTS)- and temporary threshold shift (TTS)-inducing noise exposures. Histological analysis of the cochlear tissue revealed that E2-replacement mitigated outer hair cell loss and cochlear synaptopathy following noise exposure compared to vehicle-treatment. Lastly, using fluorescent in situ hybridization, we demonstrate co-localization of estrogen receptor-2 with type-1C, high threshold spiral ganglion neurons, suggesting that the observed protection from cochlear synaptopathy may occur through E2-mediated preservation of these neurons. Taken together, these data indicate the estrogen signaling pathways may be harnessed for the prevention and treatment of NIHL.<\/jats:p>","DOI":"10.3390\/ijms222212208","type":"journal-article","created":{"date-parts":[[2021,11,11]],"date-time":"2021-11-11T23:02:41Z","timestamp":1636671761000},"page":"12208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Estradiol Protects against Noise-Induced Hearing Loss and Modulates Auditory Physiology in Female Mice"],"prefix":"10.3390","volume":"22","author":[{"given":"Benjamin","family":"Shuster","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Casserly","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Lipford","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafal","family":"Olszewski","sequence":"additional","affiliation":[{"name":"Auditory Development and Restoration Program, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9atrice","family":"Milon","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaun","family":"Viechweg","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanisa","family":"Davidson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Enoch","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"McMurray","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Rutherford","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin K.","family":"Ohlemiller","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Hoa","sequence":"additional","affiliation":[{"name":"Auditory Development and Restoration Program, National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7708-2660","authenticated-orcid":false,"given":"Didier A.","family":"Depireux","sequence":"additional","affiliation":[{"name":"Otolith Labs, Washington, DC 20036, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica A.","family":"Mong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronna","family":"Hertzano","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA"},{"name":"Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 21201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,11]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2018, June 08). Deafness and Hearing Loss. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/deafness-and-hearing-loss."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/S0140-6736(21)00516-X","article-title":"Hearing loss prevalence and years lived with disability, 1990\u20132019: Findings from the Global Burden of Disease Study 2019","volume":"397","author":"Haile","year":"2021","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1097\/MAO.0000000000001427","article-title":"Emerging Therapies for Sensorineural Hearing Loss HHS Public Access Author manuscript","volume":"38","author":"Crowson","year":"2017","journal-title":"Otol. Neurotol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.pharmthera.2019.05.003","article-title":"New molecular therapies for the treatment of hearing loss","volume":"200","author":"Ma","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s40463-017-0219-x","article-title":"Current insights in noise-induced hearing loss: A literature review of the underlying mechanism, pathophysiology, asymmetry, and management options","volume":"46","author":"Le","year":"2017","journal-title":"J. Otolaryngol. Head Neck Surg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1097\/MAO.0000000000001071","article-title":"Temporary and Permanent Noise-Induced Threshold Shifts: A Review of Basic and Clinical Observations","volume":"37","author":"Ryan","year":"2016","journal-title":"Otol. Neurotol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Liberman, M.C., Epstein, M.J., Cleveland, S.S., Wang, H., and Maison, S.F. (2016). Toward a Differential Diagnosis of Hidden Hearing Loss in Humans. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0162726"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.heares.2017.01.003","article-title":"Cochlear synaptopathy in acquired sensorineural hearing loss: Manifestations and mechanisms","volume":"349","author":"Liberman","year":"2017","journal-title":"Hear. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1152\/jn.00164.2013","article-title":"Noise-induced cochlear neuropathy is selective for fibers with low spontaneous rates","volume":"110","author":"Furman","year":"2013","journal-title":"J. Neurophysiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/j.cell.2018.07.007","article-title":"Sensory Neuron Diversity in the Inner Ear Is Shaped by Activity","volume":"174","author":"Shrestha","year":"2018","journal-title":"Cell"},{"key":"ref_11","first-page":"1","article-title":"Perceptual consequences of \u2018hidden\u2019 hearing loss","volume":"18","author":"Plack","year":"2014","journal-title":"Trends Hear."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0378-5955(99)00163-X","article-title":"Histopathological differences between temporary and permanent threshold shift","volume":"139","author":"Nordmann","year":"2000","journal-title":"Hear. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0378-5955(00)00081-2","article-title":"Noise damage in the C57BL\/CBA mouse cochlea","volume":"145","author":"Ou","year":"2000","journal-title":"Hear. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0378-5955(01)00224-6","article-title":"Differential vulnerability of basal and apical hair cells is based on intrinsic susceptibility to free radicals","volume":"155","author":"Sha","year":"2001","journal-title":"Hear. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3656","DOI":"10.1121\/1.5111870","article-title":"Sex Differences in Hearing: Probing the Role of Estrogen Signaling","volume":"145","author":"Shuster","year":"2019","journal-title":"J. Acoust. Soc. Am."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s13293-018-0171-0","article-title":"The impact of biological sex on the response to noise and otoprotective therapies against acoustic injury in mice","volume":"9","author":"Milon","year":"2018","journal-title":"Biol. Sex Differ."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"18063","DOI":"10.1038\/s41598-020-75058-w","article-title":"Integrated stress response inhibition provides sex-dependent protection against noise-induced cochlear synaptopathy","volume":"10","author":"Rouse","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.yfrne.2013.07.006","article-title":"Estrogenic modulation of auditory processing: A vertebrate comparison","volume":"34","author":"Caras","year":"2013","journal-title":"Front. Neuroendocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.heares.2008.12.009","article-title":"Functional responses of estrogen receptors in the male and female auditory system","volume":"252","author":"Charitidi","year":"2009","journal-title":"Hear. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/s00018-019-03295-y","article-title":"Auditory function and dysfunction: Estrogen makes a difference","volume":"77","author":"Delhez","year":"2019","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1097\/MAO.0000000000002507","article-title":"Sex-based Differences in Hearing Loss: Perspectives from Non-clinical Research to Clinical Outcomess","volume":"Volume 41","author":"Villavisanis","year":"2020","journal-title":"Otology and Neurotology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1172\/JCI32796","article-title":"Estrogen receptor Beta protects against acoustic trauma in mice","volume":"118","author":"Meltser","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1677\/JOE-09-0060","article-title":"Inner ear pathology and loss of hearing in estrogen receptor-beta deficient mice","volume":"201","author":"Simonoska","year":"2009","journal-title":"J. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.yfrne.2013.09.001","article-title":"Sex differences in anxiety and depression: Role of testosterone","volume":"Volume 35","author":"McHenry","year":"2014","journal-title":"Frontiers in Neuroendocrinology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3571","DOI":"10.1210\/en.2012-1340","article-title":"Minireview: Translational Animal Models of Human Menopause: Challenges and Emerging Opportunities","volume":"153","author":"Brinton","year":"2012","journal-title":"Endocrinology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.ejphar.2015.03.028","article-title":"Animal models for osteoporosis","volume":"759","author":"Komori","year":"2015","journal-title":"Eur. J. Pharm."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/B978-0-444-64032-1.00030-8","article-title":"Auditory brainstem response","volume":"Volume 160","author":"Eggermont","year":"2019","journal-title":"Handbook of Clinical Neurology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1093\/bmb\/63.1.223","article-title":"Otoacoustic emissions, their origin in cochlear function, and use","volume":"63","author":"Kemp","year":"2002","journal-title":"Br. Med. Bull."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1097\/00003446-199004000-00003","article-title":"Outer Hair Cell Electromotility and Otoacoustic Emissions","volume":"11","author":"Brownell","year":"1990","journal-title":"Ear Hear."},{"key":"ref_30","first-page":"281","article-title":"Distortion Product Otoacoustic Emissions: A Tool for Hearing Assessment and Scientific Study","volume":"103","author":"Abdala","year":"2001","journal-title":"Volta Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"316","DOI":"10.3389\/fnmol.2019.00316","article-title":"Single Cell and Single Nucleus RNA-Seq Reveal Cellular Heterogeneity and Homeostatic Regulatory Networks in Adult Mouse Stria Vascularis","volume":"12","author":"Korrapati","year":"2019","journal-title":"Front. Mol. Neurosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0378-5955(02)00279-4","article-title":"K+ cycling and the endocochlear potential","volume":"165","author":"Wangemann","year":"2002","journal-title":"Hear. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.heares.2018.01.015","article-title":"The endocochlear potential as an indicator of reticular lamina integrity after noise exposure in mice","volume":"361","author":"Ohlemiller","year":"2018","journal-title":"Hear. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.brainres.2009.02.079","article-title":"Mechanisms and genes in human strial presbycusis from animal models","volume":"1277","author":"Ohlemiller","year":"2009","journal-title":"Brain Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/0378-5955(84)90057-1","article-title":"The effects of furosemide on the endocochlear potential and auditory-nerve fiber tuning curves in cats","volume":"14","author":"Sewell","year":"1984","journal-title":"Hear. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s10162-016-0589-1","article-title":"Application of Mouse Models to Research in Hearing and Balance","volume":"17","author":"Ohlemiller","year":"2016","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.heares.2015.02.009","article-title":"Synaptopathy in the noise-exposed and aging cochlea: Primary neural degeneration in acquired sensorineural hearing loss","volume":"330","author":"Kujawa","year":"2015","journal-title":"Hear. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1007\/s101620020028","article-title":"Dynamics of Noise-Induced Cellular Injury and Repair in the Mouse Cochlea","volume":"3","author":"Wang","year":"2002","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0378-5955(92)90200-7","article-title":"A comparison of changes in the stereocilia between temporary and permanent hearing losses in acoustic trauma","volume":"62","author":"Gao","year":"1992","journal-title":"Hear. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.heares.2009.09.009","article-title":"The menopause triggers hearing decline in healthy women","volume":"259","author":"Hederstierna","year":"2010","journal-title":"Hear. Res."},{"key":"ref_41","first-page":"726","article-title":"The Association between Serum Estradiol Level and Hearing Sensitivity in Postmenopausal Women","volume":"99","author":"Kim","year":"2002","journal-title":"Obs. Gynecol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3389\/fnmol.2020.00087","article-title":"Regeneration of Cochlear Synapses by Systemic Administration of a Bisphosphonate","volume":"13","author":"Seist","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"10832","DOI":"10.1523\/JNEUROSCI.23-34-10832.2003","article-title":"CaV1.3 Channels Are Essential for Development and Presynaptic Activity of Cochlear Inner Hair Cells","volume":"23","author":"Brandt","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1152\/physrev.00003.2003","article-title":"Nongenomic Steroid Action: Controversies, Questions, and Answers","volume":"83","author":"Falkenstein","year":"2003","journal-title":"Physiol. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1073\/pnas.97.2.883","article-title":"Kinetics of exocytosis and endocytosis at the cochlear inner hair cell afferent synapse of the mouse","volume":"97","author":"Moser","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4773","DOI":"10.1523\/JNEUROSCI.4511-11.2012","article-title":"Spike Encoding of Neurotransmitter Release Timing by Spiral Ganglion Neurons of the Cochlea","volume":"32","author":"Rutherford","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1210\/me.2004-0486","article-title":"Mechanisms of Estrogen Receptor Signaling: Convergence of Genomic and Nongenomic Actions on Target Genes","volume":"19","year":"2005","journal-title":"Mol. Endocrinol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3109\/00016480903016570","article-title":"Effects of age and sex on the expression of estrogen receptor \u03b1 and \u03b2 in the mouse inner ear","volume":"130","author":"Motohashi","year":"2010","journal-title":"Acta Oto-Laryngol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0378-5955(99)00098-2","article-title":"Mapping of estrogen receptors \u03b1 and \u03b2 in the inner ear of mouse and rat","volume":"136","author":"Stenberg","year":"1999","journal-title":"Hear. Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Saito, K., and Cui, H. (2018). Emerging Roles of Estrogen-Related Receptors in the Brain: Potential Interactions with Estrogen Signaling. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041091"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"189","DOI":"10.3389\/fnins.2017.00189","article-title":"Contralateral inhibition of click- and chirp-evoked human compound action potentials","volume":"11","author":"Smith","year":"2017","journal-title":"Front. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1152\/physrev.00036.2014","article-title":"Estrogen Effects on Cognitive and Synaptic Health over the Lifecourse","volume":"95","author":"Hara","year":"2015","journal-title":"Physiol. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/j.neuroscience.2006.09.056","article-title":"Astrocyte-derived estrogen enhances synapse formation and synaptic transmission between cultured neonatal rat cortical neurons","volume":"144","author":"Hu","year":"2007","journal-title":"Neuroscience"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1523\/JNEUROSCI.1970-18.2019","article-title":"Neuron-Derived Estrogen Regulates Synaptic Plasticity and Memory","volume":"39","author":"Lu","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.neuroscience.2011.11.035","article-title":"Estradiol acts via estrogen receptors alpha and beta on pathways important for synaptic plasticity in the mouse hippocampal formation","volume":"202","author":"Tsuda","year":"2012","journal-title":"Neuroscience"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"15362","DOI":"10.1038\/s41598-019-51724-6","article-title":"Protection from noise-induced cochlear synaptopathy by virally mediated overexpression of NT3","volume":"9","author":"Hashimoto","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"24907","DOI":"10.1038\/srep24907","article-title":"Round-window delivery of neurotrophin 3 regenerates cochlear synapses after acoustic overexposure","volume":"6","author":"Suzuki","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/nrn3856","article-title":"The neuroprotective actions of oestradiol and oestrogen receptors","volume":"16","author":"Arevalo","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1124\/pr.109.002071","article-title":"Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines","volume":"62","author":"Gillies","year":"2010","journal-title":"Pharm. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"FDing, F., Yao, J., Zhao, L., Mao, Z., Chen, S., and Brinton, R.D. (2013). Ovariectomy Induces a Shift in Fuel Availability and Metabolism in the Hippocampus of the Female Transgenic Model of Familial Alzheimer\u2019s. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059825"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1023\/A:1007025219044","article-title":"Gonadal hormones affect neuronal vulnerability to excitotoxin-induced degeneration","volume":"28","author":"Azcoitia","year":"1999","journal-title":"J. Neurocytol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4434","DOI":"10.1523\/JNEUROSCI.2228-18.2019","article-title":"Vesicular Glutamatergic Transmission in Noise-Induced Loss and Repair of Cochlear Ribbon Synapses","volume":"39","author":"Kim","year":"2019","journal-title":"J. Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1097\/00001756-199806220-00037","article-title":"Excitotoxicity and repair of cochlear synapses after noise-trauma induced hearing loss","volume":"9","author":"Puel","year":"1998","journal-title":"NeuroReport"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3828","DOI":"10.1073\/pnas.1914247117","article-title":"Protection of cochlear synapses from noise-induced excitotoxic trauma by blockade of Ca2+-permeable AMPA receptors","volume":"117","author":"Hu","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.mce.2013.12.017","article-title":"Non-feminizing estrogens: A novel neuroprotective therapy","volume":"389","author":"Petrone","year":"2014","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.jsbmb.2013.12.011","article-title":"Use of SERMs for treatment in postmenopausal women","volume":"142","author":"Pinkerton","year":"2014","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.pbb.2004.04.022","article-title":"Sex dimorphisms in the neuroprotective effects of estrogen in an animal model of Parkinson\u2019s disease","volume":"78","author":"Gillies","year":"2004","journal-title":"Pharm. Biochem. Behav."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.brainres.2007.08.036","article-title":"Estrogen suppresses brain mitochondrial oxidative stress in female and male rats","volume":"1176","author":"Razmara","year":"2007","journal-title":"Brain Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1161\/01.STR.30.8.1665","article-title":"17\u03b2-Estradiol Reduces Stroke Injury in Estrogen-Deficient Female Animals","volume":"30","author":"Rusa","year":"1999","journal-title":"Stroke"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1161\/01.STR.29.8.1666","article-title":"Estrogen-Mediated Neuroprotection after Experimental Stroke in Male Rats","volume":"29","author":"Toung","year":"1998","journal-title":"Stroke"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/nn.2834","article-title":"Reframing sexual differentiation of the brain","volume":"14","author":"McCarthy","year":"2011","journal-title":"Nat. Neurosci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1080\/14992027.2016.1192693","article-title":"A polymorphism in human estrogen-related receptor beta (ESRR\u03b2) predicts audiometric temporary threshold shift","volume":"55","author":"Bhatt","year":"2016","journal-title":"Int. J. Audiol"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1016\/j.neurobiolaging.2013.02.009","article-title":"Estrogen-related receptor gamma and hearing function: Evidence of a role in humans and mice","volume":"34","author":"Nolan","year":"2013","journal-title":"Neurobiol. Aging"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.1038\/ejhg.2016.64","article-title":"Estrogen-related receptor gamma implicated in a phenotype including hearing loss and mild developmental delay","volume":"24","author":"Schilit","year":"2016","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e535","DOI":"10.1016\/j.ejmg.2011.06.008","article-title":"A novel missense mutation in the ESRRB gene causes DFNB35 hearing loss in a Tunisian family","volume":"54","author":"Ayedi","year":"2011","journal-title":"Eur. J. Med. Genet."},{"key":"ref_76","first-page":"294","article-title":"Influence of hormonal changes on audiologic examination in normal ovarian cycle females: An analytic study","volume":"20","author":"Adriztina","year":"2016","journal-title":"Int. Arch. Otorhinolaryngol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e22626","DOI":"10.1002\/jcla.22626","article-title":"Correlation between auditory-vestibular functions and estrogen levels in postmenopausal patients with Meniere\u2019s disease","volume":"33","author":"Jian","year":"2019","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"7509","DOI":"10.1523\/JNEUROSCI.5138-14.2015","article-title":"Aging after Noise Exposure: Acceleration of Cochlear Synaptopathy in \u201cRecovered\u201d Ears","volume":"35","author":"Fernandez","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"6357","DOI":"10.1523\/JNEUROSCI.0937-20.2020","article-title":"Age-Related Hearing Loss Is Dominated by Damage to Inner Ear Sensory Cells, Not the Cellular Battery That Powers Them","volume":"40","author":"Wu","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.ejps.2014.09.002","article-title":"Raloxifene protects against seizures and neurodegeneration in a mouse model mimicking epilepsy in postmenopausal woman","volume":"65","author":"Pottoo","year":"2014","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/S0010-7824(80)80018-7","article-title":"A comparison of the pharmacokinetic properties of three estradiol esters","volume":"21","author":"Driowo","year":"1980","journal-title":"Contraception"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/0009-8981(94)90116-3","article-title":"Non-specific steroidal esterase activity and distribution in human and other mammalian tissues","volume":"224","author":"Jeppson","year":"1994","journal-title":"Clin. Chim. Acta"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Wangemann, P., Itza, E.M., Albrecht, B., Wu, T., Jabba, S.V., Maganti, R.J., Lee, J.H., Everett, L.A., Wall, S.M., and E Royaux, I. (2004). Loss of KCNJ10 protein expression abolishes endocochlear potential and causes deafness in Pendred syndrome mouse model. BMC Med., 2.","DOI":"10.1186\/1741-7015-2-30"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"F1345","DOI":"10.1152\/ajprenal.00487.2006","article-title":"Loss of cochlear HCO3\u2212 secretion causes deafness via endolymphatic acidification and inhibition of Ca2+ reabsorption in a Pendred syndrome mouse model","volume":"292","author":"Wangemann","year":"2007","journal-title":"Am. J. Physiol.-Ren. Physiol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2976","DOI":"10.1523\/JNEUROSCI.2278-19.2020","article-title":"Noncoding Microdeletion in Mouse Hgf Disrupts Neural Crest Migration into the Stria Vascularis, Reduces the Endocochlear Potential, and Suggests the Neuropathology for Human Nonsyndromic Deafness DFNB39","volume":"40","author":"Morell","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s10162-010-0228-1","article-title":"Divergent Aging Characteristics in CBA\/J and CBA\/CaJ Mouse Cochleae","volume":"11","author":"Ohlemiller","year":"2010","journal-title":"J. Assoc. Res. Otolaryngol."},{"key":"ref_87","unstructured":"(2020, September 29). Mouse Cochlear Dissection. Available online: https:\/\/vimeo.com\/144531710."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/22\/12208\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:28:43Z","timestamp":1760167723000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/22\/12208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,11]]},"references-count":87,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["ijms222212208"],"URL":"https:\/\/doi.org\/10.3390\/ijms222212208","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,11]]}}}