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Otol Neurotol. 2018 Mar;39(3):e173-e180. doi: 10.1097/MAO.0000000000001717.

Long-term Administration of Salicylate-induced Changes in BDNF Expression and CREB Phosphorylation in the Auditory Cortex of Rats.

Yi B1,2,3, Wu C1,2,3, Shi R1,2,3, Han K1,2,3, Sheng H1,2,3, Li B1,2,3, Mei L4, Wang X1,2,3, Huang Z1,2,3, Wu H1,2,3.

Author information

1
Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital.
2
Laboratory of Auditory Neuroscience, Ear Institute, Shanghai Jiaotong University School of Medicine.
3
Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases.
4
Department of Otorhinolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Abstract

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.

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