{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T06:34:48Z","timestamp":1770186888534,"version":"3.49.0"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research foundation","doi-asserted-by":"crossref","award":["RS-2023-00208042, RS-2023-00210067"],"award-info":[{"award-number":["RS-2023-00208042, RS-2023-00210067"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea","award":["RS-2025-25459502"],"award-info":[{"award-number":["RS-2025-25459502"]}]},{"name":"SNU Creative-Pioneering Researchers Program","award":["800-20250440"],"award-info":[{"award-number":["800-20250440"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study investigated the effects of fluoxetine on noise-induced injuries to the cochlea and auditory nerve, with a focus on its impact on perineuronal nets (PNNs) and gene expression changes in the ventral cochlear nuclei (VCN).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Sprague-Dawley rats were exposed to white noise at 115 dB SPL for 3 hours per day over 3 weeks. After measuring auditory brainstem response (ABR) thresholds, rats were treated with fluoxetine (10 mg\/kg) for 19 days. Four groups were included (vehicle, fluoxetine, noise\u2009+\u2009vehicle, and noise\u2009+\u2009fluoxetine; n\u2009=\u200910 per group). ABR measurements, analysis of extracellular baskets in cochlear ribbon synapses and PNNs, and RNA sequencing of the VCN were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Following fluoxetine treatment, noise-exposed rats (noise\u2009+\u2009fluoxetine group) showed hearing thresholds comparable to those in the noise\u2009+\u2009vehicle group. Both noise-exposed groups exhibited cochlear hair cell loss and disorganization. Extracellular baskets surrounding cochlear ribbon synapses were significantly reduced in noise\u2009+\u2009vehicle rats and were not restored in noise\u2009+\u2009fluoxetine rats. Aggrecan expression in the VCN was reduced in the noise\u2009+\u2009fluoxetine group. RNA sequencing revealed upregulation of genes including\n                      <jats:italic>Mal, Fos, Rapgef3, Papss2, Adamts4,<\/jats:italic>\n                      and\n                      <jats:italic>Heph,<\/jats:italic>\n                      and downregulation of genes such as\n                      <jats:italic>Pde5a, Kcnma1, Nr4a1, Dlgap3, Slc18a2,<\/jats:italic>\n                      and\n                      <jats:italic>Dgkg<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Fluoxetine exerted only modest, 4 kHz\u2011restricted improvements in ABR thresholds and did not restore cochlear structure or normal hearing following noise\u2011induced hearing loss. However, it induced distinct transcriptional alterations in the VCN and modulated the extracellular environment, suggesting a potential role in neural remodeling rather than direct auditory restoration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0341746","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T18:36:07Z","timestamp":1770143767000},"page":"e0341746","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fluoxetine minimally affects hearing loss but induces gene expression changes in the cochlear nuclei after noise 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