Mahmoudian Saeid, Jouzdani Ali Fathi, Nazeri Ahmadreza, Bagherian Kasra, Beiranvand Mohadeseh, Akbarnejad Zeinab
ENT and Head and Neck Research Center and Department, The Five Senses Health Institute, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Neuroscience and Artificial Intelligence Research Group (NAIRG), Department of Neuroscience, School of Science and Advanced Technologies in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
IBRO Neurosci Rep. 2024 Nov 13;17:407-414. doi: 10.1016/j.ibneur.2024.11.007. eCollection 2024 Dec.
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.
鉴于耳鸣和焦虑在患者中普遍存在，了解增加焦虑的机制至关重要。神经连接蛋白2（NLGN2）是一种与焦虑相关的蛋白质，近年来备受关注。另一方面，脑源性神经营养因子（BDNF）影响各种神经递质系统、神经肽和细胞内信号通路。这些神经化学系统若失衡，可能导致焦虑行为。这是第一项研究杏仁核中蛋白质表达变化是否与耳鸣患者的高度焦虑相关的研究。在使用声惊吓的间隙前脉冲抑制（GPIAS）和前脉冲抑制（PPI）诱导并确认大鼠耳鸣后，采用高架十字迷宫（EPM）和旷场试验（OFT）评估两组的焦虑水平。随后，从两组收集杏仁核组织样本，分析NLGN2和BDNF蛋白表达。耳鸣组给予水杨酸钠后GPIAS评分降低，而PPI评分未改变。此外，在两项行为测试中，耳鸣组的焦虑水平均高于对照组。此外，与对照组相比，水杨酸钠诱导的耳鸣大鼠杏仁核中NLGN2蛋白表达增加，而BDNF蛋白表达降低。这些发现表明，杏仁核中NLGN2增加和BDNF蛋白水平降低导致耳鸣相关焦虑，并将这些蛋白质确定为耳鸣的潜在治疗靶点。
