{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:47:48Z","timestamp":1791323268341,"version":"4.3.1"},"reference-count":85,"publisher":"Society for Neuroscience","issue":"13","license":[{"start":{"date-parts":[[2006,9,29]],"date-time":"2006-09-29T00:00:00Z","timestamp":1159488000000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2006,3,29]]},"abstract":"<jats:p>Degeneration of the spiral ganglion neurons (SGNs) of the auditory nerve occurs with age and in response to acoustic injury. Histopathological observations suggest that the neural degeneration often begins with an excitotoxic process affecting the afferent dendrites under the inner hair cells (IHCs), however, little is known about the sequence of cellular or molecular events mediating this excitotoxicity. Nuclear factor \u03baB (NF\u03baB) is a transcription factor involved in regulating inflammatory responses and apoptosis in many cell types. NF\u03baB is also associated with intracellular calcium regulation, an important factor in neuronal excitotoxicity. Here, we provide evidence that NF\u03baB can play a central role in the degeneration of SGNs. Mice lacking the p50 subunit of NF\u03baB (p50<jats:sup>\u2212\/\u2212<\/jats:sup>mice) showed an accelerated hearing loss with age that was highly associated with an exacerbated excitotoxic-like damage in afferent dendrites under IHCs and an accelerated loss of SGNs. Also, as evidenced by immunostaining intensity, calcium-buffering proteins were significantly elevated in SGNs of the p50<jats:sup>\u2212\/\u2212<\/jats:sup>mice. Finally, the knock-out mice exhibited an increased sensitivity to low-level noise exposure. The accelerated hearing loss and neural degeneration with age in the p50<jats:sup>\u2212\/\u2212<\/jats:sup>mice occurred in the absence of concomitant hair cell loss and decline of the endocochlear potential. These results indicate that NF\u03baB activity plays an important role in protecting the primary auditory neurons from excitotoxic damage and age-related degeneration. A possible mechanism underlying this protection is that the NF\u03baB activity may help to maintain calcium homeostasis in SGNs.<\/jats:p>","DOI":"10.1523\/jneurosci.2488-05.2006","type":"journal-article","created":{"date-parts":[[2006,3,29]],"date-time":"2006-03-29T19:42:57Z","timestamp":1143661377000},"page":"3541-3550","source":"Crossref","is-referenced-by-count":89,"title":["Nuclear Factor \u03baB Deficiency Is Associated with Auditory Nerve Degeneration and Increased Noise-Induced Hearing Loss"],"prefix":"10.1523","volume":"26","author":[{"given":"Hainan","family":"Lang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley A.","family":"Schulte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daohong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Smythe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel S.","family":"Spicer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Schmiedt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2006,3,29]]},"reference":[{"key":"2023041303173253000_26.13.3541.1","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1523\/JNEUROSCI.22-04-01385.2002","volume":"22","year":"(2002)","journal-title":"J Neurosci"},{"key":"2023041303173253000_26.13.3541.2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0155-04.2004"},{"key":"2023041303173253000_26.13.3541.3","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1159\/000276714","volume":"57","year":"(1995)","journal-title":"ORL J Otorhinolaryngol Relat Spec"},{"key":"2023041303173253000_26.13.3541.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4160(03)00141-6"},{"key":"2023041303173253000_26.13.3541.5","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5277-04.2005"},{"key":"2023041303173253000_26.13.3541.6","doi-asserted-by":"crossref","first-page":"8466","DOI":"10.1523\/JNEUROSCI.22-19-08466.2002","volume":"22","year":"(2002)","journal-title":"J Neurosci"},{"key":"2023041303173253000_26.13.3541.7","doi-asserted-by":"crossref","first-page":"4668","DOI":"10.1523\/JNEUROSCI.21-13-04668.2001","volume":"21","year":"(2001)","journal-title":"J Neurosci"},{"key":"2023041303173253000_26.13.3541.8","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200211000-00028"},{"key":"2023041303173253000_26.13.3541.9","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1523\/JNEUROSCI.23-03-00777.2003","volume":"23","year":"(2003)","journal-title":"J Neurosci"},{"key":"2023041303173253000_26.13.3541.10","doi-asserted-by":"publisher","DOI":"10.1007\/s004410051207"},{"key":"2023041303173253000_26.13.3541.11","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410923200"},{"key":"2023041303173253000_26.13.3541.12","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.53.030191.002531"},{"key":"2023041303173253000_26.13.3541.13","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(90)90091-H"},{"key":"2023041303173253000_26.13.3541.14","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0378-5955(00)00077-0","volume":"145","year":"(2000)","journal-title":"Hear Res"},{"key":"2023041303173253000_26.13.3541.15","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(97)13364-X"},{"key":"2023041303173253000_26.13.3541.16","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(95)00201-4"},{"key":"2023041303173253000_26.13.3541.17","doi-asserted-by":"crossref","unstructured":"Ding D, McFadden SL, Salvi RJ (2001) Cochlear hair cell densities and inner-ear staining techniques. In: Handbook of mouse auditory research (Willott JF, ed.) pp. 189\u2013204. New York: CRC.","DOI":"10.1201\/9781420038736.ch13"},{"key":"2023041303173253000_26.13.3541.18","doi-asserted-by":"publisher","DOI":"10.1023\/A:1015434524040"},{"key":"2023041303173253000_26.13.3541.19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.13.7597"},{"key":"2023041303173253000_26.13.3541.20","doi-asserted-by":"publisher","DOI":"10.1016\/S0074-7696(08)62695-9"},{"key":"2023041303173253000_26.13.3541.21","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101315200"},{"key":"2023041303173253000_26.13.3541.22","doi-asserted-by":"crossref","unstructured":"Green SHNeurotrophic signaling by membrane electrical activity in spiral ganglion neurons. In: Cell and molecular biology of the ear (Lim DJ, ed.) pp. 165\u2013182. New York: Kluwer Academic\/Plenum.","DOI":"10.1007\/978-1-4615-4223-0_13"},{"key":"2023041303173253000_26.13.3541.23","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.20.12341"},{"key":"2023041303173253000_26.13.3541.24","doi-asserted-by":"crossref","first-page":"8750","DOI":"10.1523\/JNEUROSCI.20-23-08750.2000","volume":"20","year":"(2000)","journal-title":"J Neurosci"},{"key":"2023041303173253000_26.13.3541.25","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.10551"},{"key":"2023041303173253000_26.13.3541.26","doi-asserted-by":"crossref","first-page":"7361","DOI":"10.1523\/JNEUROSCI.18-18-07361.1998","volume":"18","year":"(1998)","journal-title":"J Neurosci"},{"key":"2023041303173253000_26.13.3541.27","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1007\/s101620010075","volume":"2","year":"(2001)","journal-title":"J Assoc Res Otolaryngol"},{"key":"2023041303173253000_26.13.3541.28","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-002-3036-4"},{"key":"2023041303173253000_26.13.3541.29","doi-asserted-by":"publisher","DOI":"10.1121\/1.392798"},{"key":"2023041303173253000_26.13.3541.30","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)00494-P"},{"key":"2023041303173253000_26.13.3541.31","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(03)00076-5"},{"key":"2023041303173253000_26.13.3541.32","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1007\/s10162-002-2037-7","volume":"4","year":"(2003)","journal-title":"J Assoc Res Otolaryngol"},{"key":"2023041303173253000_26.13.3541.33","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20392"},{"key":"2023041303173253000_26.13.3541.34","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.14.6.3981"},{"key":"2023041303173253000_26.13.3541.35","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2002.7967"},{"key":"2023041303173253000_26.13.3541.36","doi-asserted-by":"publisher","DOI":"10.1002\/cne.901880306"},{"key":"2023041303173253000_26.13.3541.37","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(03)00138-2"},{"key":"2023041303173253000_26.13.3541.38","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1177\/000348947608500605","volume":"85","year":"(1976)","journal-title":"Ann Otol Rhinol Laryngol"},{"key":"2023041303173253000_26.13.3541.39","unstructured":"Kimura RS (1984) Sensory and accessory epithelia of the cochlea. In: Ultrastructural atlas of the inner ear (Friedmann I, Ballantyne J, eds) pp. 101\u2013132. London: Butterworths."},{"key":"2023041303173253000_26.13.3541.40","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.02014.x"},{"key":"2023041303173253000_26.13.3541.41","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(02)00552-X"},{"key":"2023041303173253000_26.13.3541.42","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-004-5021-6"},{"key":"2023041303173253000_26.13.3541.43","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(88)90018-4"},{"key":"2023041303173253000_26.13.3541.44","doi-asserted-by":"publisher","DOI":"10.1121\/1.1772395"},{"key":"2023041303173253000_26.13.3541.45","unstructured":"Liberman MC, Mulroy MJ (1982) Acute and chronic effects of acoustic trauma: cochlear pathology and auditory nerve pathophysiology. In: New perspectives on noise-induced hearing loss (Hamernik RP, Henderson D, Salvi R, eds) pp. 105\u2013151. New York: Raven."},{"key":"2023041303173253000_26.13.3541.46","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903010309"},{"key":"2023041303173253000_26.13.3541.47","doi-asserted-by":"publisher","DOI":"10.1385\/NMM:3:2:65"},{"key":"2023041303173253000_26.13.3541.48","doi-asserted-by":"publisher","DOI":"10.1385\/JMN:17:2:205"},{"key":"2023041303173253000_26.13.3541.49","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2000.740443.x"},{"key":"2023041303173253000_26.13.3541.50","doi-asserted-by":"publisher","DOI":"10.1038\/nn1110"},{"key":"2023041303173253000_26.13.3541.51","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19980713)396:4<442::AID-CNE3>3.0.CO;2-1"},{"key":"2023041303173253000_26.13.3541.52","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19981207)402:1<129::AID-CNE9>3.0.CO;2-A"},{"key":"2023041303173253000_26.13.3541.53","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/0378-5955(94)90152-X","volume":"81","year":"(1994)","journal-title":"Hear Res"},{"key":"2023041303173253000_26.13.3541.54","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1007\/s10162-005-0006-7","volume":"6","year":"(2005)","journal-title":"J Assoc Res Otolaryngol"},{"key":"2023041303173253000_26.13.3541.55","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20326"},{"key":"2023041303173253000_26.13.3541.56","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2001.7817"},{"key":"2023041303173253000_26.13.3541.57","unstructured":"Puel JL, D\u2019Aldin CG, Safieddine S, Eybalin M, Pujol R (1996) Excitotoxicity and plasticity of IHC-auditory nerve contributes to both temporary and permanent threshold shift. In: Scientific basis of noise-induced hearing loss (Axelsson A, Borchgrevink H, Hamernik RP, Hellstrom PA, Henderson D, Salvi RJ, eds) pp. 36\u201342. New York: Thieme."},{"key":"2023041303173253000_26.13.3541.58","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199806220-00037"},{"key":"2023041303173253000_26.13.3541.59","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb08646.x"},{"key":"2023041303173253000_26.13.3541.60","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(85)90006-1"},{"key":"2023041303173253000_26.13.3541.61","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(03)00344-7"},{"key":"2023041303173253000_26.13.3541.62","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(99)00179-3"},{"key":"2023041303173253000_26.13.3541.63","doi-asserted-by":"publisher","DOI":"10.1002\/cne.900990105"},{"key":"2023041303173253000_26.13.3541.64","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1002\/j.1460-2075.1986.tb04243.x","volume":"5","year":"(1986)","journal-title":"EMBO J"},{"key":"2023041303173253000_26.13.3541.65","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(83)90031-X"},{"key":"2023041303173253000_26.13.3541.66","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(00)00183-0"},{"key":"2023041303173253000_26.13.3541.67","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90415-8"},{"key":"2023041303173253000_26.13.3541.68","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(93)90053-4"},{"key":"2023041303173253000_26.13.3541.69","doi-asserted-by":"publisher","DOI":"10.1002\/syn.20026"},{"key":"2023041303173253000_26.13.3541.70","first-page":"530","volume":"25","year":"(2002)","journal-title":"Assoc Res Otolaryngol Abstr"},{"key":"2023041303173253000_26.13.3541.71","doi-asserted-by":"publisher","DOI":"10.3109\/00016486909125448"},{"key":"2023041303173253000_26.13.3541.72","doi-asserted-by":"publisher","DOI":"10.3109\/00016487109125346"},{"key":"2023041303173253000_26.13.3541.73","doi-asserted-by":"publisher","DOI":"10.1121\/1.418315"},{"key":"2023041303173253000_26.13.3541.74","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0733-04.2004"},{"key":"2023041303173253000_26.13.3541.75","doi-asserted-by":"publisher","DOI":"10.1007\/s10162-004-5050-1"},{"key":"2023041303173253000_26.13.3541.76","doi-asserted-by":"publisher","DOI":"10.1007\/s101620020028"},{"key":"2023041303173253000_26.13.3541.77","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(99)00204-X"},{"key":"2023041303173253000_26.13.3541.78","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1152\/jn.1986.56.2.391","volume":"56","year":"(1986)","journal-title":"J Neurophysiol"},{"key":"2023041303173253000_26.13.3541.79","first-page":"19","volume":"37","year":"(2002)","journal-title":"Zhonghua Er Bi Yan Hou Ke Za Zhi"},{"key":"2023041303173253000_26.13.3541.80","doi-asserted-by":"crossref","first-page":"8856","DOI":"10.1523\/JNEUROSCI.19-20-08856.1999","volume":"19","year":"(1999)","journal-title":"J Neurosci"},{"key":"2023041303173253000_26.13.3541.81","doi-asserted-by":"publisher","DOI":"10.1385\/JMN:15:1:31"},{"key":"2023041303173253000_26.13.3541.82","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(01)00267-2"},{"key":"2023041303173253000_26.13.3541.83","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(99)00003-9"},{"key":"2023041303173253000_26.13.3541.84","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-5955(96)00188-8"},{"key":"2023041303173253000_26.13.3541.85","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1999.tb08647.x"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.2488-05.2006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,13]],"date-time":"2023-04-13T17:20:39Z","timestamp":1681406439000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.2488-05.2006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,3,29]]},"references-count":85,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2006,3,29]]},"published-print":{"date-parts":[[2006,3,29]]}},"alternative-id":["10.1523\/JNEUROSCI.2488-05.2006"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.2488-05.2006","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,3,29]]}}}