{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:19:13Z","timestamp":1790075953167,"version":"4.0.1"},"reference-count":86,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T00:00:00Z","timestamp":1706140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondation Gueules Cass\u00e9es","award":["65-2022"],"award-info":[{"award-number":["65-2022"]}]},{"name":"Fondation Gueules Cass\u00e9es","award":["200760"],"award-info":[{"award-number":["200760"]}]},{"name":"Fondation Gueules Cass\u00e9es","award":["NIH NIGMS T32-GM007337"],"award-info":[{"award-number":["NIH NIGMS T32-GM007337"]}]},{"name":"Fondation Gueules Cass\u00e9es","award":["NIH NIDCD F31-DC020371"],"award-info":[{"award-number":["NIH NIDCD F31-DC020371"]}]},{"name":"AB science company","award":["65-2022"],"award-info":[{"award-number":["65-2022"]}]},{"name":"AB science company","award":["200760"],"award-info":[{"award-number":["200760"]}]},{"name":"AB science company","award":["NIH NIGMS T32-GM007337"],"award-info":[{"award-number":["NIH NIGMS T32-GM007337"]}]},{"name":"AB science company","award":["NIH NIDCD F31-DC020371"],"award-info":[{"award-number":["NIH NIDCD F31-DC020371"]}]},{"name":"Chateaubriand Fellowship of the Office for Science &amp; Technology of the Embassy of France in the United States","award":["65-2022"],"award-info":[{"award-number":["65-2022"]}]},{"name":"Chateaubriand Fellowship of the Office for Science &amp; Technology of the Embassy of France in the United States","award":["200760"],"award-info":[{"award-number":["200760"]}]},{"name":"Chateaubriand Fellowship of the Office for Science &amp; Technology of the Embassy of France in the United States","award":["NIH NIGMS T32-GM007337"],"award-info":[{"award-number":["NIH NIGMS T32-GM007337"]}]},{"name":"Chateaubriand Fellowship of the Office for Science &amp; Technology of the Embassy of France in the United States","award":["NIH NIDCD F31-DC020371"],"award-info":[{"award-number":["NIH NIDCD F31-DC020371"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The disruption of the synaptic connection between the sensory inner hair cells (IHCs) and the auditory nerve fiber terminals of the type I spiral ganglion neurons (SGN) has been observed early in several auditory pathologies (e.g., noise-induced or ototoxic drug-induced or age-related hearing loss). It has been suggested that glutamate excitotoxicity may be an inciting element in the degenerative cascade observed in these pathological cochlear conditions. Moreover, oxidative damage induced by free hydroxyl radicals and nitric oxide may dramatically enhance cochlear damage induced by glutamate excitotoxicity. To investigate the underlying molecular mechanisms involved in cochlear excitotoxicity, we examined the molecular basis responsible for kainic acid (KA, a full agonist of AMPA\/KA-preferring glutamate receptors)-induced IHC synapse loss and degeneration of the terminals of the type I spiral ganglion afferent neurons using a cochlear explant culture from P3 mouse pups. Our results demonstrated that disruption of the synaptic connection between IHCs and SGNs induced increased levels of oxidative stress, as well as altered both mitochondrial function and neurotrophin signaling pathways. Additionally, the application of exogenous antioxidants and neurotrophins (NT3, BDNF, and small molecule TrkB agonists) clearly increases synaptogenesis. These results suggest that understanding the molecular pathways involved in cochlear excitotoxicity is of crucial importance for the future clinical trials of drug interventions for auditory synaptopathies.<\/jats:p>","DOI":"10.3390\/antiox13020149","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T03:59:42Z","timestamp":1706155182000},"page":"149","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Oxidative Stress Plays an Important Role in Glutamatergic Excitotoxicity-Induced Cochlear Synaptopathy: Implication for Therapeutic Molecules Screening"],"prefix":"10.3390","volume":"13","author":[{"given":"Anissa Rym","family":"Saidia","sequence":"first","affiliation":[{"name":"Institute for Neurosciences of Montpellier (INM), INSERM U1298, University Montpellier, 34295 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Fran\u00e7ois","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences of Montpellier (INM), INSERM U1298, University Montpellier, 34295 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5535-8195","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Casas","sequence":"additional","affiliation":[{"name":"INRA, UMR 866 Dynamique Musculaire et M\u00e9tabolisme, 34060 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilana","family":"Mechaly","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences of Montpellier (INM), INSERM U1298, University Montpellier, 34295 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Venteo","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences of Montpellier (INM), INSERM U1298, University Montpellier, 34295 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2890-3458","authenticated-orcid":false,"given":"Joseph T.","family":"Veechi","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences of Montpellier (INM), INSERM U1298, University Montpellier, 34295 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Ruel","sequence":"additional","affiliation":[{"name":"Centre de Recherche en CardioVasculaire et Nutrition, Aix-Marseille Universit\u00e9-INSERM, 1263-INRAE 1260, 13385 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3772-5190","authenticated-orcid":false,"given":"Jean-Luc","family":"Puel","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences of Montpellier (INM), INSERM U1298, University Montpellier, 34295 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2670-719X","authenticated-orcid":false,"given":"Jing","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute for Neurosciences of Montpellier (INM), INSERM U1298, University Montpellier, 34295 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0306-4522(93)90389-W","article-title":"Dopaminergic Lateral Efferent Innervation of the Guinea-Pig Cochlea: Immunoelectron Microscopy of Catecholamine-Synthesizing Enzymes and Effect of 6-Hydroxydopamine","volume":"54","author":"Eybalin","year":"1993","journal-title":"Neuroscience"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"235","DOI":"10.3109\/00016487209138937","article-title":"Innervation Densities of the Cochlea","volume":"73","author":"Spoendlin","year":"1972","journal-title":"Acta Otolaryngol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/0378-5955(82)90023-5","article-title":"Type II Cochlear Ganglion Cells in the Chinchilla","volume":"8","author":"Ruggero","year":"1982","journal-title":"Hear. 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