{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:11:22Z","timestamp":1760058682485,"version":"build-2065373602"},"reference-count":51,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Commission Action HORIZON 2020","award":["764604\/ESR11"],"award-info":[{"award-number":["764604\/ESR11"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: Inner hair cell (IHC) ribbon synapses are the initial synapses in the auditory pathway, comprising presynaptic ribbons and postsynaptic glutamate receptors on the peripheral afferent fibers. The excitatory neurotransmitter glutamate primarily signals through AMPA-type heterotetrameric receptors (AMPARs), composed of GluR1, GluR2, GluR3, and GluR4 subunits. Research shows that corticosterone affects AMPA receptor subunits in the central nervous system. The present study investigates the effects of corticosterone on AMPA receptor subunits in the murine cochlea. Methods: Cochlear explants were isolated from male and female C57BL\/6 pups (postnatal days 4\u20135), treated for 20 min with 100 nM corticosterone, and cultured for an additional 24 h. The concentration of AMPAR protein subunits was quantified using an ELISA assay, while gene expression was analyzed using RT-PCR. The synaptic localization patterns of GluR2 and Ribeye were examined using immunofluorescence and confocal microscopy. Results: Male C57BL\/6 mice have a significantly greater basal concentration of the GluR2 subunit than females and more GluR2 puncta per IHC than females. Corticosterone increases the size of Ribeye in males and increases twofold GluR2\/Ribeye colocalization in the apical region of females. Conclusions: Exposure of membranous cochleae to corticosterone induces changes consistent with neuroplasticity in the auditory periphery. The observed effect is sex-dependent.<\/jats:p>","DOI":"10.3390\/brainsci15050441","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T06:18:02Z","timestamp":1745475482000},"page":"441","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Size and Localization of Ribeye and GluR2 in the Auditory Inner Hair Cell Synapse of C57BL\/6 Mice Are Affected by Short-Pulse Corticosterone in a Sex-Dependent Manner"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4616-4954","authenticated-orcid":false,"given":"Ewa","family":"Domarecka","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi","family":"Olze","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9292-6606","authenticated-orcid":false,"given":"Agnieszka J.","family":"Szczepek","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Charit\u00e9-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, 10117 Berlin, Germany"},{"name":"Faculty of Medicine and Health Sciences, University of Zielona G\u00f3ra, 65-046 Zielona G\u00f3ra, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/nn796","article-title":"Transmitter release at the hair cell ribbon synapse","volume":"5","author":"Glowatzki","year":"2002","journal-title":"Nat. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1038\/nn.2293","article-title":"Tuning of synapse number, structure and function in the cochlea","volume":"12","author":"Meyer","year":"2009","journal-title":"Nat. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1002\/syn.21812","article-title":"Resolving the structure of inner ear ribbon synapses with STED microscopy","volume":"69","author":"Rutherford","year":"2015","journal-title":"Synapse"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1016\/j.biopsych.2020.12.031","article-title":"The Acute Stress Response in the Multiomic Era","volume":"89","author":"Waag","year":"2021","journal-title":"Biol. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nrn1683","article-title":"Stress and the brain: From adaptation to disease","volume":"6","author":"Holsboer","year":"2005","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/nrn3138","article-title":"The stressed synapse: The impact of stress and glucocorticoids on glutamate transmission","volume":"13","author":"Popoli","year":"2011","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Sarabdjitsingh, R.A., Pasricha, N., Smeets, J.A., Kerkhofs, A., Mikasova, L., Karst, H., Groc, L., and Jo\u00ebls, M. (2016). Hippocampal Fast Glutamatergic Transmission Is Transiently Regulated by Corticosterone Pulsatility. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0145858"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Lee, M.T., Peng, W.-H., Kan, H.-W., Wu, C.-C., Wang, D.-W., and Ho, Y.-C. (2022). Neurobiology of Depression: Chronic Stress Alters the Glutamatergic System in the Brain\u2014Focusing on AMPA Receptor. Biomedicines, 10.","DOI":"10.3390\/biomedicines10051005"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1523\/JNEUROSCI.18-07-02685.1998","article-title":"Corticosteroid regulation of ion channel conductances and mRNA levels in individual hippocampal CA1 neurons","volume":"18","author":"Nair","year":"1998","journal-title":"J. Neurosci. Off. J. Soc. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Martin, S., Henley, J.M., Holman, D., Zhou, M., Wiegert, O., van Spronsen, M., Jo\u00ebls, M., Hoogenraad, C.C., and Krugers, H.J. (2009). Corticosterone alters AMPAR mobility and facilitates bidirectional synaptic plasticity. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0004714"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Edlund, E., Domarecka, E., Olze, H., and Szczepek, A. (2025). A Scoping Review of Corticosterone-Induced Changes in Ionotropic Glutamate Receptor Levels and Localization in the Rodent Brain: Implications for the Auditory System. Brain Sci., 15.","DOI":"10.3390\/brainsci15020110"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.neuroscience.2013.05.043","article-title":"Stress and excitatory synapses: From health to disease","volume":"248","author":"Timmermans","year":"2013","journal-title":"Neuroscience"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Torrisi, S.A., Rizzo, S., Laudani, S., Ieraci, A., Drago, F., and Leggio, G.M. (2023). Acute stress alters recognition memory and AMPA\/NMDA receptor subunits in a sex-dependent manner. Neurobiol. Stress, 25.","DOI":"10.1016\/j.ynstr.2023.100545"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1021\/acschemneuro.5b00096","article-title":"Gender differences in spatial learning, synaptic activity, and long-term potentiation in the hippocampus in rats: Molecular mechanisms","volume":"6","author":"Monfort","year":"2015","journal-title":"ACS Chem. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wickens, M.M., Bangasser, D.A., and Briand, L.A. (2018). Sex Differences in Psychiatric Disease: A Focus on the Glutamate System. Front. Mol. Neurosci., 11.","DOI":"10.3389\/fnmol.2018.00197"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Szczepek, A.J., Dietz, G.P.H., Reich, U., Hegend, O., Olze, H., and Mazurek, B. (2018). Differences in Stress-Induced Modulation of the Auditory System Between Wistar and Lewis Rats. Front. Neurosci., 12.","DOI":"10.3389\/fnins.2018.00828"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/BF00660742","article-title":"Effect of emotional stress on hearing","volume":"228","author":"Muchnik","year":"1980","journal-title":"Arch. Otorhinolaryngol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Yu, Y., Szczepek, A.J., Haupt, H., and Mazurek, B. (2009). Geldanamycin induces production of heat shock protein 70 and partially attenuates ototoxicity caused by gentamicin in the organ of Corti explants. J. Biomed. Sci., 16.","DOI":"10.1186\/1423-0127-16-79"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1038\/79910","article-title":"Corticosteroid actions in hippocampus require DNA binding of glucocorticoid receptor homodimers","volume":"3","author":"Karst","year":"2000","journal-title":"Nat. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/S0306-4522(02)00483-9","article-title":"Corticosterone and stress reduce synaptic potentiation in mouse hippocampal slices with mild stimulation","volume":"115","author":"Alfarez","year":"2002","journal-title":"Neuroscience"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/nn.2150","article-title":"The stress hormone corticosterone conditions AMPAR surface trafficking and synaptic potentiation","volume":"11","author":"Groc","year":"2008","journal-title":"Nat. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bassiouni, M., Smorodchenko, A., Olze, H., and Szczepek, A.J. (2023). Identification and Characterization of TMEM119-Positive Cells in the Postnatal and Adult Murine Cochlea. Brain Sci., 13.","DOI":"10.3390\/brainsci13030516"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1007\/s00109-006-0097-6","article-title":"Quantitative real-time RT-PCR data analysis: Current concepts and the novel \u201cgene expression\u2019s CT difference\u201d formula","volume":"84","author":"Schefe","year":"2006","journal-title":"J. Mol. Med."},{"key":"ref_24","first-page":"1","article-title":"GluA2-Containing AMPA Receptors Distinguish Ribbon-Associated from Ribbonless Afferent Contacts on Rat Cochlear Hair Cells","volume":"3","author":"Liu","year":"2016","journal-title":"eNeuro"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"100544","DOI":"10.1016\/j.xpro.2021.100544","article-title":"Preparation of the intact rodent organ of Corti for RNAscope and immunolabeling, confocal microscopy, and quantitative analysis","volume":"2","author":"Reijntjes","year":"2021","journal-title":"STAR Protoc."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Clancy, S., Xie, N., Muttikkal, T.E., Wang, J., Fateh, E., Smith, M., Wilson, P., Smith, M., Hogan, A., and Sutherland, A. (2024). Rac1 and Nectin3 are essential for PCP-directed axon guidance in the peripheral auditory system. bioRxiv.","DOI":"10.1101\/2024.06.05.597585"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ymeth.2016.11.016","article-title":"DiAna, an ImageJ tool for object-based 3D co-localization and distance analysis","volume":"115","author":"Gilles","year":"2017","journal-title":"Methods"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/j.1365-2826.2006.01413.x","article-title":"Acute activation of hippocampal glucocorticoid receptors results in different waves of gene expression throughout time","volume":"18","author":"Morsink","year":"2006","journal-title":"J. Neuroendocr."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lozier, N.R., Muscio, S., Pal, I., Cai, H.M., and Rubio, M.E. (2023). Sex differences in glutamate AMPA receptor subunits mRNA with fast gating kinetics in the mouse cochlea. Front. Syst. Neurosci., 17.","DOI":"10.3389\/fnsys.2023.1100505"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6415","DOI":"10.1073\/pnas.1812029116","article-title":"Mapping developmental maturation of inner hair cell ribbon synapses in the apical mouse cochlea","volume":"116","author":"Michanski","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/1749-8104-7-38","article-title":"Synaptic profiles during neurite extension, refinement and retraction in the developing cochlea","volume":"7","author":"Huang","year":"2012","journal-title":"Neural Dev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1002\/cne.10638","article-title":"AMPA, kainate, and NMDA receptor densities in the hippocampus of untreated male rats and females in estrus and diestrus","volume":"459","author":"Bidmon","year":"2003","journal-title":"J. Comp. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"109187","DOI":"10.1016\/j.heares.2025.109187","article-title":"Gonad-derived steroid hormones mediate a sex difference in the maturation of auditory encoding in the cochlea from adolescence to early adulthood in C57BL\/6J mice","volume":"457","author":"Lozier","year":"2025","journal-title":"Hear. Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ismail Mohamad, N., Santra, P., Park, Y., Matthews, I.R., Taketa, E., and Chan, D.K. (2024). Synaptic ribbon dynamics after noise exposure in the hearing cochlea. Commun. Biol., 7.","DOI":"10.1038\/s42003-024-06067-y"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4339","DOI":"10.1113\/JP280018","article-title":"Pathophysiological changes in inner hair cell ribbon synapses in the ageing mammalian cochlea","volume":"598","author":"Jeng","year":"2020","journal-title":"J. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e30241","DOI":"10.7554\/eLife.30241","article-title":"The presynaptic ribbon maintains vesicle populations at the hair cell afferent fiber synapse","volume":"7","author":"Becker","year":"2018","journal-title":"eLife"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3700","DOI":"10.1128\/MCB.00150-13","article-title":"Brain-derived neurotrophic factor signaling rewrites the glucocorticoid transcriptome via glucocorticoid receptor phosphorylation","volume":"33","author":"Lambert","year":"2013","journal-title":"Mol. Cell. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"14265","DOI":"10.1073\/pnas.1411216111","article-title":"Ultradian corticosterone pulses balance glutamatergic transmission and synaptic plasticity","volume":"111","author":"Sarabdjitsingh","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1177\/0269881111424930","article-title":"Combined \u03b2-adrenergic and corticosteroid receptor activation regulates AMPA receptor function in hippocampal neurons","volume":"26","author":"Zhou","year":"2012","journal-title":"J. Psychopharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1523\/JNEUROSCI.3389-10.2011","article-title":"Opposing gradients of ribbon size and AMPA receptor expression underlie sensitivity differences among cochlear-nerve\/hair-cell synapses","volume":"31","author":"Liberman","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3005","DOI":"10.1096\/fj.201701041RRR","article-title":"The glucocorticoid antagonist mifepristone attenuates sound-induced long-term deficits in auditory nerve response and central auditory processing in female rats","volume":"32","author":"Singer","year":"2018","journal-title":"Faseb J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4430","DOI":"10.1210\/en.2006-0260","article-title":"Glucocorticoid receptor and nuclear factor-kappa B interactions in restraint stress-mediated protection against acoustic trauma","volume":"147","author":"Tahera","year":"2006","journal-title":"Endocrinology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/j.neuroscience.2005.07.032","article-title":"Chronic stress impairs acoustic conditioning more than visual conditioning in rats: Morphological and behavioural evidence","volume":"135","author":"Terreros","year":"2005","journal-title":"Neuroscience"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.heares.2009.10.006","article-title":"Stress induces transient auditory hypersensitivity in rats","volume":"259","author":"Mazurek","year":"2010","journal-title":"Hear. Res."},{"key":"ref_45","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_46","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1111\/j.1460-9568.2004.03772.x","article-title":"Transient Ca2+-permeable AMPA receptors in postnatal rat primary auditory neurons","volume":"20","author":"Eybalin","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13041-019-0442-7","article-title":"Structural plasticity of the hippocampus in response to estrogens in female rodents","volume":"12","author":"Sheppard","year":"2019","journal-title":"Mol. Brain"},{"key":"ref_48","first-page":"55704","article-title":"Neonatal Murine Cochlear Explant Technique as an In Vitro Screening Tool in Hearing Research","volume":"124","author":"Landegger","year":"2017","journal-title":"J. Vis. Exp."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1089\/hum.2016.053","article-title":"Identification of Adeno-Associated Viral Vectors That Target Neonatal and Adult Mammalian Inner Ear Cell Subtypes","volume":"27","author":"Shu","year":"2016","journal-title":"Hum. Gene Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/7854_2020_215","article-title":"Neurobiology of Stress-Induced Tinnitus","volume":"51","author":"Szczepek","year":"2021","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1016\/j.cub.2019.06.057","article-title":"Circadian Regulation of Cochlear Sensitivity to Noise by Circulating Glucocorticoids","volume":"29","author":"Cederroth","year":"2019","journal-title":"Curr. Biol."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/15\/5\/441\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:20:37Z","timestamp":1760030437000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/15\/5\/441"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,24]]},"references-count":51,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,5]]}},"alternative-id":["brainsci15050441"],"URL":"https:\/\/doi.org\/10.3390\/brainsci15050441","relation":{},"ISSN":["2076-3425"],"issn-type":[{"type":"electronic","value":"2076-3425"}],"subject":[],"published":{"date-parts":[[2025,4,24]]}}}