3,6'-Dithiothalidomide Reduces Tinnitus Phenotype in Two Different Mouse Preclinical Models of Tinnitus

Sergio Gonzalez-Gonzalez, Chantal Cazevieille
2020 Journal of community and preventive medicine  
Tinnitus is the perception of a sound in the absence of external stimulation. Tinnitus is a common consequence of damage to the auditory periphery, affecting around 5-12% of the population and inducing intolerable discomfort. Today, no treatment exists to cure tinnitus. From an electrophysiology point of view, tinnitus leads to auditory brainstem responses (ABRs) wave modifications and spontaneous activity changes of the primary auditory cortex (PAC) in human and rodents. Moreover, plasma
more » ... eover, plasma brain-derived neurotrophic factor (BDNF) levels vary with the severity of tinnitus, suggesting that plasma BDNF level can be used as a biomarker to objectively evaluate tinnitus in rodent and humans. Several publications suggested that tinnitus is closely related to auditory system inflammation and proinflammatory cytokine TNF-α. Results: we evaluated the efficacy of a novel thalidomide-based TNF-α lowering agent, the 3,6'-dithiothalidomide (TLD) in two different preclinical models of tinnitus. We observed that TLD treatment increased the % of startle GAP suppression, increased ABR wave I amplitude and decreased wave IV latency, decreased spontaneous activity of PAC, and significantly decrease plasma BDNF concentration in the salicylate-induced and noise-induced tinnitus mouse models. Conclusions: Our data confirm that proinflammatory cytokines are directly linked to tinnitus phenotype suggesting that inflammatory pharmacological modulators could be a promising therapy targeting tinnitus disorder.
doi:10.33309/2638-7719.030102 fatcat:bvdpkbsacbhrxmo4p37f57ye54