PMID- 29342042 OWN - NLM STAT- MEDLINE DCOM- 20190923 LR - 20190923 IS - 1537-4505 (Electronic) IS - 1531-7129 (Print) IS - 1531-7129 (Linking) VI - 39 IP - 3 DP - 2018 Mar TI - Long-term Administration of Salicylate-induced Changes in BDNF Expression and CREB Phosphorylation in the Auditory Cortex of Rats. PG - e173-e180 LID - 10.1097/MAO.0000000000001717 [doi] AB - HYPOTHESIS: We investigated whether salicylate induces tinnitus through alteration of the expression levels of brain-derived neurotrophic factor (BDNF), proBDNF, tyrosine kinase receptor B (TrkB), cAMP-responsive element-binding protein (CREB), and phosphorylated CREB (p-CREB) in the auditory cortex (AC). BACKGROUND: Salicylate medication is frequently used for long-term treatment in clinical settings, but it may cause reversible tinnitus. Salicylate-induced tinnitus is associated with changes related to central auditory neuroplasticity. Our previous studies revealed enhanced neural activity and ultrastructural synaptic changes in the central auditory system after long-term salicylate administration. However, the underlying mechanisms remained unclear. METHODS: Salicylate-induced tinnitus-like behavior in rats was confirmed using gap prepulse inhibition of acoustic startle and prepulse inhibition testing, followed by comparison of the expression levels of BDNF, proBDNF, TrkB, CREB, and p-CREB. Synaptic ultrastructure was observed under a transmission electron microscope. RESULTS: BDNF and p-CREB were upregulated along with ultrastructural changes at the synapses in the AC of rats treated chronically with salicylate (p < 0.05, compared with control group). These changes returned to normal after 14 days of recovery (p > 0.05). CONCLUSION: Long-term administration of salicylate increased BDNF expression and CREB activation, upregulated synaptic efficacy, and changed synaptic ultrastructure in the AC. There may be a relationship between these factors and the mechanism of tinnitus. FAU - Yi, Bin AU - Yi B AD - Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital. AD - Laboratory of Auditory Neuroscience, Ear Institute, Shanghai Jiaotong University School of Medicine. AD - Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases. FAU - Wu, Cong AU - Wu C AD - Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital. AD - Laboratory of Auditory Neuroscience, Ear Institute, Shanghai Jiaotong University School of Medicine. AD - Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases. FAU - Shi, Runjie AU - Shi R AD - Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital. AD - Laboratory of Auditory Neuroscience, Ear Institute, Shanghai Jiaotong University School of Medicine. AD - Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases. FAU - Han, Kun AU - Han K AD - Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital. AD - Laboratory of Auditory Neuroscience, Ear Institute, Shanghai Jiaotong University School of Medicine. AD - Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases. FAU - Sheng, Haibin AU - Sheng H AD - Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital. AD - Laboratory of Auditory Neuroscience, Ear Institute, Shanghai Jiaotong University School of Medicine. AD - Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases. FAU - Li, Bei AU - Li B AD - Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital. AD - Laboratory of Auditory Neuroscience, Ear Institute, Shanghai Jiaotong University School of Medicine. AD - Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases. FAU - Mei, Ling AU - Mei L AD - Department of Otorhinolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. FAU - Wang, Xueling AU - Wang X AD - Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital. AD - Laboratory of Auditory Neuroscience, Ear Institute, Shanghai Jiaotong University School of Medicine. AD - Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases. FAU - Huang, Zhiwu AU - Huang Z AD - Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital. AD - Laboratory of Auditory Neuroscience, Ear Institute, Shanghai Jiaotong University School of Medicine. AD - Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases. FAU - Wu, Hao AU - Wu H AD - Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital. AD - Laboratory of Auditory Neuroscience, Ear Institute, Shanghai Jiaotong University School of Medicine. AD - Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Otol Neurotol JT - Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology JID - 100961504 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (Salicylates) SB - IM MH - Animals MH - Auditory Cortex/*drug effects/metabolism/pathology MH - Brain-Derived Neurotrophic Factor/*drug effects MH - Cyclic AMP Response Element-Binding Protein/*drug effects MH - Male MH - Phosphorylation/drug effects MH - Rats MH - Rats, Sprague-Dawley MH - Salicylates/*toxicity MH - Synapses/drug effects/pathology MH - Tinnitus PMC - PMC5821486 COIS- The authors disclose no conflicts of interest. EDAT- 2018/01/18 06:00 MHDA- 2019/09/24 06:00 PMCR- 2018/02/21 CRDT- 2018/01/18 06:00 PHST- 2018/01/18 06:00 [pubmed] PHST- 2019/09/24 06:00 [medline] PHST- 2018/01/18 06:00 [entrez] PHST- 2018/02/21 00:00 [pmc-release] AID - ON-17-188 [pii] AID - 10.1097/MAO.0000000000001717 [doi] PST - ppublish SO - Otol Neurotol. 2018 Mar;39(3):e173-e180. doi: 10.1097/MAO.0000000000001717.