Role of microRNA‑375‑3p‑mediated regulation in tinnitus development

Abstract

changes in the dorsal cochlear nucleus (dcN) following exposure to noise play an important role in the development of tinnitus. As the development of several diseases is known to be associated with microRNAs (miRNAs/miRs), the aim of the present study was to identify the miRNAs that may be implicated in pathogenic changes in the dcN, resulting in tinnitus. A previously developed tinnitus animal model was used for this study. The study consisted of four stages, including identification of candidate miRNAs involved in tinnitus development using miRNA microarray analysis, validation of miRNA expression using reverse transcription-quantitative PcR (RT-qPcR), evaluation of the effects of candidate miRNA overexpression on tinnitus development through injection of a candidate miRNA mimic or mimic negative control, and target prediction of candidate miRNAs using mRNA microarray analysis and western blotting. The miRNA microarray and RT-qPcR analyses revealed that miR-375-3p expression was significantly reduced in the tinnitus group compared with that in the non-tinnitus group. Additionally, miR-375-3p overexpression via injection of miR-375-3p mimic reduced the proportion of animals with persistent tinnitus. Based on mRNA microarray and western blot analyses, connective tissue growth factor (CTGF) was identified as a potential target for miR-375-3p. Thus, it was inferred that cTGF downregulation by miR-375-3p may weaken with the decrease in miRNA expression, and the increased pro-apoptotic activity of cTGF may result in more severe neuronal damage, contributing to tinnitus development. These findings are expected to contribute significantly to the development of a novel therapeutic approach to tinnitus, thereby bringing about a significant breakthrough in the treatment of this potentially debilitating condition.

MicroRNA-375-3p Alleviates Salicylate-Induced Neuronal Injury by Targeting ELAVL4 in Tinnitus

“…A previous study indicated the downregulation of miR-375-3p in rats with tinnitus and that overexpressing miR-375-3p may prevent the persistence of tinnitus in rats. 21 In this study, we further explored the function of miR-375-3p in regulating salicylate-triggered neuron injury. Consistent with previous evidence, our results depicted that miR-375-3p level was decreased in salicylate-treated SH-SY5Y neurons in comparison to that in control cells.…”

“…20 Moreover, Han et al proposed that miR-375-3p is downregulated in rats with tinnitus compared with that in control rats and overexpressing miR-375-3p may prevent the persistence of tinnitus in rats. 21 Nonetheless, the molecular mechanisms of miR-375-3p underlying tinnitus pathogenesis remain unclarified.…”

Differential Expression of miRNAs and Their Predicted Target Pathways in Cochlear Nucleus Following Chronic Noise Exposure in Rats

“…Hearing levels were estimated using auditory brainstem response (ABR) thresholds. Two months after noise exposure, all rats were euthanized and the cochleae and CN were dissected [ 43 ].…”

Investigation of Some Ion Channel Expressions in Cochlear Nucleus of Tinnitus Induced Rats

“…The cochlear nucleus is the first center in the auditory pathway that processes acoustic signals from direct projections of the auditory nerve. In addition to cellular changes, changes at the molecular levels could be responsible for the pathophysiology of tinnitus [17][18][19] . Y. ÜSTÜNDAĞ, G. DİNÇ, R. BAL In the last decade, animal research has clearly demonstrated that tinnitus is a pathology of synaptic plasticity 20 .…”