Molecular Network of Tinnitus Focusing on BDNF Signal and Autophagy in Auditory Cells

Abstract

Objectives: Recent studies show that the expression of brain-derived neurotrophic factor (BDNF) is decreasing in patients with depression and severe tinnitus. However, the relationship between the incidence of tinnitus and the role of BDNF remains unclear in auditory cells. The aim of this study is to consider the molecular network of tinnitus focusing on BDNF signal and autophagy in auditory cells. Methods: We used auditory cell line (HEI-OC1) in this study. Tunicamycin was used as endoplasmic reticulum (ER) stress. The viability of HEI-OC1 was determined by cell viability assays. Morphological observation was performed under transmission electron microscope (TEM). Western blot analysis was performed. Results: The cell viability after treatment of tunicamycin was decreased in dose- and time-dependent matter. Autophagosomes and autolysososmes were confirmed into the cytoplasm of HEI-OC1 under TEM. The expression of LC3-II was increased in HEI-OC1 after treatment of tunicamycin. These results mean that autophagy was consistently induced in tunicamycin-treated cells. The expression of CHOP was decreased after peaking at 12 hours after the treatment of tunicamycin. The expression of BDNF, which has the potential to become a biomarker of tinnitus, and calcium-dependent activator protein for secretion 2 (CAPS2) that promotes BDNF section, were decreased in tunicamycin-treated cells. The expression of Bcl-2 that control apoptosis and Beclin1 that regulate autophagy were decreased in tunicamycin-treated cells. Conclusions: Our results lead to the suggestion that the autophagy-mediated regulation of cell death and molecular network focusing on BDNF signal play a major part of the incidence of tinnitus.