Molecular and Cellular Biochemistry

, Volume 448, Issue 1–2, pp 71–76 | Cite as

Up-regulation of Ca2+/CaMKII/CREB signaling in salicylate-induced tinnitus in rats

  • Jiuhan Zhao
  • Biao Wang
  • Xiaohong Wang
  • Xiuli ShangEmail author


The purpose of the study was to investigate the changes of Ca2+/calmodulin-dependent protein kinases II (CaMKII)/cAMP response element-binding protein (CREB) signaling pathway in a rat tinnitus model. Eighteen Wistar rats were randomly divided into three groups: normal control (NC), normal saline (NS), and tinnitus model (TM) groups. Tinnitus model was induced by intraperitoneal injection of salicylate. The concentration of intracellular calcium level in auditory cortex cells was determined using Fura-2 acetoxymethyl ester (Fura-2 AM) method with fluorospectrophotometer. Expressions of calmodulin (CaM), N-methyl-d-aspartate receptor 2B subunit (NR2B), calcium-calmodulin kinase II (CaMKII), and cAMP response element-binding protein (CREB) were detected with Western blot. Tinnitus model was successfully established by the intraperitoneal administration of salicylate in rats. Compared with rats in NC and NS groups, salicylate administration significantly elevated CaM, NR2B, phospho-CaMKII and phospho-CREB expression in auditory cortex from tinnitus model group (p < 0.05), and the free intracellular Ca2+ concentrations (p < 0.05). Our data reveal that salicylate administration causes tinnitus symptoms and elevates Ca2+/CaMKII/CREB signaling pathway in auditory cortex cells. Our study likely provides a new understanding of the development of tinnitus.


Tinnitus Auditory cortex Ca2+/calmodulin-dependent kinase II cAMP response element-binding protein 


Compliance with ethical standards

Conflict of interest

All the authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Jiuhan Zhao
    • 1
  • Biao Wang
    • 2
  • Xiaohong Wang
    • 1
  • Xiuli Shang
    • 1
    Email author
  1. 1.Department of NeurologyFirst Affiliated Hospital of China Medical UniversityShenyangChina
  2. 2.Department of Biochemistry and Molecular BiologyChina Medical UniversityShenyangChina

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