{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T17:01:37Z","timestamp":1788800497320,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,1,22]],"date-time":"2015-01-22T00:00:00Z","timestamp":1421884800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Ministry of Health, Labor, and Welfare of Japan","award":["H16-kankakuki-006"],"award-info":[{"award-number":["H16-kankakuki-006"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:p>The sigma\u20101 receptor, which is expressed throughout the brain, provides physiological benefits that include higher brain function. The sigma\u20101 receptor functions as a chaperone in the endoplasmic reticulum and may control cell death and regeneration within the central nervous system. Cutamesine (1\u2010(3,4\u2010dimethoxyphenethyl)\u22124\u2010(3\u2010phenylpropyl) piperazine dihydrochloride) is a ligand selective for this receptor and may mediate neuroprotective effects in the context of neurodegenerative disease. We therefore assessed whether cutamesine protects the inner ear from noise\u2010induced or aging\u2010associated hearing loss. Immunohistochemistry and Western blotting revealed that the sigma\u20101 receptor is present in adult cochlea. We treated mice with 0, 3, or 30 mg\/kg cutamesine from 10 days before noise exposure until the end of the study. All subjects were exposed to a 120\u2010dB, 4\u2010kHz octave\u2010band noise for 2 hr. We assessed auditory thresholds by measuring the auditory\u2010evoked brainstem responses at 4, 8, and 16 kHz, prior to and 1 week, 1 month, or 3 months following noise exposure. For the aging study, measurements were made before treatment was initiated and after 3 or 9 months of cutamesine treatment. Damage to fibrocytes within the cochlear spiral limbus was assessed by quantitative histology. Cutamesine significantly reduced threshold shifts and cell death within the spiral limbus in response to intense noise. These effects were not dose or time dependent. Conversely, cutamesine did not prevent aging\u2010associated hearing loss. These results suggest that cutamesine reduces noise\u2010induced hearing loss and cochlear damage during the acute phase that follows exposure to an intense noise. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jnr.23543","type":"journal-article","created":{"date-parts":[[2015,1,23]],"date-time":"2015-01-23T05:05:52Z","timestamp":1421989552000},"page":"788-795","source":"Crossref","is-referenced-by-count":12,"title":["Neuroprotective effects of cutamesine, a ligand of the sigma\u20101 receptor chaperone, against noise\u2010induced hearing loss"],"prefix":"10.1002","volume":"93","author":[{"given":"Daisuke","family":"Yamashita","sequence":"first","affiliation":[{"name":"Department of Otolaryngology School of Medicine, Kobe University Kobe Japan"},{"name":"Laboratory of Auditory Disorders Division of Hearing and Balance Research, National Institute of Sensory Organs, National Tokyo Medical Center Tokyo Japan"},{"name":"Department of Otolaryngology School of Medicine, Keio 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