PMID- 24583017 OWN - NLM STAT- MEDLINE DCOM- 20141007 LR - 20211021 IS - 1879-0445 (Electronic) IS - 0960-9822 (Print) IS - 0960-9822 (Linking) VI - 24 IP - 6 DP - 2014 Mar 17 TI - TrkB-mediated protection against circadian sensitivity to noise trauma in the murine cochlea. PG - 658-63 LID - S0960-9822(14)00080-3 [pii] LID - 10.1016/j.cub.2014.01.047 [doi] AB - Noise-induced hearing loss (NIHL) is a debilitating sensory impairment affecting 10%-15% of the population, caused primarily through damage to the sensory hair cells or to the auditory neurons. Once lost, these never regenerate [1], and no effective drugs are available [2, 3]. Emerging evidence points toward an important contribution of synaptic ribbons in the long-term coupling of the inner hair cell and afferent neuron synapse to maintain hearing [4]. Here we show in nocturnal mice that night noise overexposure triggers permanent hearing loss, whereas mice overexposed during the day recover to normal auditory thresholds. In view of this time-dependent sensitivity, we identified a self-sustained circadian rhythm in the isolated cochlea, as evidenced by circadian expression of clock genes and ample PERIOD2::LUCIFERASE oscillations, originating mainly from the primary auditory neurons and hair cells. The transcripts of the otoprotecting brain-derived neurotrophic factor (BDNF) showed higher levels in response to day noise versus night noise, suggesting that BDNF-mediated signaling regulates noise sensitivity throughout the day. Administration of a selective BDNF receptor, tropomyosin-related kinase type B (TrkB), in the night protected the inner hair cell's synaptic ribbons and subsequent full recovery of hearing thresholds after night noise overexposure. The TrkB agonist shifted the phase and boosted the amplitude of circadian rhythms in the isolated cochlea. These findings highlight the coupling of circadian rhythmicity and the TrkB receptor for the successful prevention and treatment of NIHL. CI - Copyright (c) 2014 Elsevier Ltd. All rights reserved. FAU - Meltser, Inna AU - Meltser I AD - Department of Physiology and Pharmacology, Karolinska Institutet, 17177 Stockholm, Sweden. FAU - Cederroth, Christopher R AU - Cederroth CR AD - Department of Physiology and Pharmacology, Karolinska Institutet, 17177 Stockholm, Sweden. FAU - Basinou, Vasiliki AU - Basinou V AD - Department of Physiology and Pharmacology, Karolinska Institutet, 17177 Stockholm, Sweden. FAU - Savelyev, Sergey AU - Savelyev S AD - Department of Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden. FAU - Lundkvist, Gabriella S AU - Lundkvist GS AD - Department of Physiology and Pharmacology, Karolinska Institutet, 17177 Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden. FAU - Canlon, Barbara AU - Canlon B AD - Department of Physiology and Pharmacology, Karolinska Institutet, 17177 Stockholm, Sweden. Electronic address: barbara.canlon@ki.se. LA - eng GR - R21 DC013172/DC/NIDCD NIH HHS/United States GR - R21DC013172/DC/NIDCD NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20140227 PL - England TA - Curr Biol JT - Current biology : CB JID - 9107782 RN - 0 (7,8-dihydroxyflavanone) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Flavanones) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.10.1 (Receptor, trkB) SB - IM CIN - Curr Biol. 2014 Mar 17;24(6):R232-4. PMID: 24650909 EIN - Curr Biol. 2020 Nov 16;30(22):4547. PMID: 33202221 MH - Animals MH - Brain-Derived Neurotrophic Factor/physiology MH - Circadian Rhythm/*physiology MH - Cochlea/drug effects/*physiology MH - Flavanones/pharmacology MH - Hair Cells, Auditory/physiology MH - Hearing/physiology MH - Hearing Loss, Noise-Induced/physiopathology MH - Male MH - Mice MH - Mice, Inbred CBA MH - Noise/*adverse effects MH - Protein Kinases/*physiology MH - Receptor, trkB/physiology PMC - PMC3962718 MID - NIHMS560516 COIS- COMPETING INTEREST The authors disclose that there are no competing financial interests. EDAT- 2014/03/04 06:00 MHDA- 2014/10/08 06:00 PMCR- 2015/03/17 CRDT- 2014/03/04 06:00 PHST- 2013/08/30 00:00 [received] PHST- 2013/12/20 00:00 [revised] PHST- 2014/01/21 00:00 [accepted] PHST- 2014/03/04 06:00 [entrez] PHST- 2014/03/04 06:00 [pubmed] PHST- 2014/10/08 06:00 [medline] PHST- 2015/03/17 00:00 [pmc-release] AID - S0960-9822(14)00080-3 [pii] AID - 10.1016/j.cub.2014.01.047 [doi] PST - ppublish SO - Curr Biol. 2014 Mar 17;24(6):658-63. doi: 10.1016/j.cub.2014.01.047. Epub 2014 Feb 27.