Changes in the Numbers of Ribbon Synapses and Expression of RIBEYE in Salicylate-Induced Tinnitus

Abstract

Background: This study was performed to explore the mechanism underlying tinnitus by investigating the changes in the synaptic ribbons and RIBEYE expression in cochlear inner hair cells in salicylate-induced tinnitus. Methods: C57BL/6J mice were injected with salicylate (350 mg/kg) for 10 days and grouped. Behavioral procedures were performed to assess whether the animals experienced tinnitus. The specific presynaptic RIBEYE protein and non-specific postsynaptic glutamate receptor 2&3 protein in basilar membrane samples were examined by immunofluorescent labeling. RT-PCR and Western blot assays were used to examine RIBEYE expression. Serial sections were used to build three-dimensional models using 3ds MAX software to evaluate the changes in the synaptic ribbons. Results: The administration of salicylate increased false positives in the behavioral procedure from 3 d to 10 d. The membrane profiles of inner hair cells in all mice were intact. The number of synaptic ribbons in the salicylate group increased on the 7^th d and decreased on the 9^th and 10^th d. mRNA and protein expression of RIBEYE were initially up-regulated and later down-regulated by injecting salicylate for 10 consecutive days. Conclusion: This change in the ribbon synapses of cochlear inner hair cells in salicylate-induced mice might serve as a compensatory mechanism in the early stages of ototoxicity and contribute to tinnitus later. The alteration of RIBEYE expression could be responsible for the changes in the morphology of ribbon synapses and for salicylate-induced tinnitus.

Cortical Tonotopic Map Changes in Humans Are Larger in Hearing Loss Than in Additional Tinnitus

“…However, the differences observed between the hearingimpaired participants with tinnitus and those without tinnitus may be due to both cochlear and central differences. Recent evidence suggests that tinnitus is associated with both reduced ribbon synapse density in the cochlea (Rüttiger et al, 2013;Zhang et al, 2014) and reduced ARC expression in the cortex (Rüttiger et al, 2013;Singer et al, 2013). With the measures of the present study (i.e., pure tone audiometry and MRI), it is not possible to identify differences in cochlear pathology between the hearing loss groups.…”

A New Statistical Approach for the Evaluation of Gap-prepulse Inhibition of the Acoustic Startle Reflex (GPIAS) for Tinnitus Assessment

“…Despite this high prevalence and the tinnitus-associated distress of affected patients, which in severe cases may experience insomnia, psychological disorders like depression, the inability to work, or even commit suicide (Coles, 1984 ; Lewis et al, 1994 ; Langguth et al, 2011 ), there still is no effective cure for the condition, because all tinnitus research faces one central problem: Whereas the existence of a tinnitus percept can unequivocally be determined in human patients (one can simply ask them; cf. e.g., Pantev et al, 2012 ; Elgoyhen et al, 2015 ; Husain, 2016 ; Leaver et al, 2016 ), this is only unsatisfactorily possible in animal models for tinnitus (Von Der Behrens, 2014 ; Zhang et al, 2014 ; Galazyuk and Hebert, 2015 ; Brozoski and Bauer, 2016 ). On the other hand, the exact mechanisms within the auditory system that lead to the development of tinnitus are still unknown and hard to identify, since invasive neurophysiological methods that are essential for such research are only available in animal models but not in humans.…”

Central Nervous Activity upon Systemic Salicylate Application in Animals with Kanamycin-Induced Hearing Loss - A Manganese-Enhanced MRI (MEMRI) Study

“…Salicylate markedly reduces the cochlear blood flow by vasoconstriction [ 17 ]. Furthermore, changes in IHC synaptic morphology occur [ 18 ] with hair cell resting potential modified through a reduction in outward potassium currents [ 19 , 20 ]. This blocks IHC function, leading in turn to a decreased neurotransmission.…”