Alterations in Neuroligin-2 and BDNF proteins associated with anxiety-like behavior in salicylate-induced tinnitus rats

Given the high prevalence of tinnitus and anxiety among patients, understanding the mechanisms that increase anxiety is crucial. Neuroligin 2 (NLGN2) is an anxiety-related protein that has received much attention in recent years. On the other hand, the Brain-Derived Neurotrophic Factor (BDNF) affects various neurotransmitter systems, neuropeptides, and intracellular signaling pathways. These are neurochemical systems that, if out of balance, could lead to anxiety behavior. This is the first study to investigate whether changes in protein expression in the amygdala nucleus are associated with high anxiety in tinnitus. After inducing and confirming tinnitus in rats using gap-prepulse inhibition of the acoustic startle (GPIAS) and Pre-pulse inhibition (PPI), the Elevated Plus Maze (EPM) and the Open Field Test (OFT) were used to assess anxiety levels in both groups. Subsequently, amygdala tissue samples were collected from both groups and analyzed for NLGN2 and BDNF protein expression. The GPIAS score decreased following sodium salicylate administration in the tinnitus group, while the PPI score did not change. Additionally, the tinnitus group exhibited higher anxiety levels than the control group in both behavioral tests. Moreover, NLGN2 protein expression was increased in the amygdala nucleus of sodium salicylate-induced tinnitus rats compared to controls, while BDNF protein expression was reduced. These findings suggest that increased NLGN2 and decreased BDNF protein levels in the amygdala nucleus contribute to tinnitus-related anxiety and identify these proteins as potential therapeutic targets for tinnitus.