背景:氧化还原失衡和炎症已被认为是听觉系统损害的主要机制,导致功能改变和听力损失。小胶质细胞和星形胶质细胞在介导中枢神经系统的氧化/炎症损伤中起着至关重要的作用。神经胶质细胞在听觉损伤中的作用尚不清楚。
目的:在这里,我们研究了神经胶质介导的对听觉通路外周和中枢结构毒性损伤的反应,即,耳蜗和听觉皮层(ACx),在暴露于苯乙烯的大鼠中,一种具有众所周知的OTO/神经毒性的挥发性化合物。
方法:雄性成年Wistar大鼠用苯乙烯处理(每天400mg/kg,持续3周,5/天一周)。电生理学,形态学,我们对耳蜗和ACx进行了免疫荧光和分子分析,以评估苯乙烯在听觉系统中诱导的臭氧/神经毒性的潜在机制.
结果:我们表明,苯乙烯诱导的卵/神经毒性损伤增加了耳蜗和ACx的氧化应激。这与巨噬细胞和神经胶质细胞活化有关,炎症标志物表达增加(即,促炎细胞因子和趋化因子受体)以及连接蛋白(Cxs)和pannexin(Panx)表达的改变,可能是小胶质细胞/星形胶质细胞网络失调的原因。具体来说,我们发现Cx26和Cx30在耳蜗中下调,和高水平的Cx43和Panx1在ACx。
结论:总的来说,我们的研究结果为免疫和神经胶质细胞活化在苯乙烯诱导的听觉系统周围和中枢水平的氧化/炎症损伤中的作用提供了新的证据。还涉及间隙连接网络的改变。我们的数据表明,靶向神经胶质细胞和连接蛋白/pannexin表达可能有助于减轻听觉系统的氧化/炎症损伤。
BACKGROUND: Redox imbalance and inflammation have been proposed as the principal mechanisms of damage in the auditory system, resulting in functional alterations and hearing loss. Microglia and astrocytes play a crucial role in mediating oxidative/inflammatory injury in the central nervous system; however, the role of glial cells in the auditory damage is still elusive.
OBJECTIVE: Here we investigated glial-mediated responses to toxic injury in peripheral and central structures of the auditory pathway, i.e., the cochlea and the auditory cortex (ACx), in rats exposed to
styrene, a volatile compound with well-known oto/neurotoxic properties.
METHODS: Male adult Wistar rats were treated with
styrene (400 mg/kg daily for 3 weeks, 5/days a week). Electrophysiological, morphological, immunofluorescence and molecular analyses were performed in both the cochlea and the ACx to evaluate the mechanisms underlying
styrene-induced oto/neurotoxicity in the auditory system.
RESULTS: We showed that the oto/neurotoxic insult induced by
styrene increases oxidative stress in both cochlea and ACx. This was associated with macrophages and glial cell activation, increased expression of inflammatory markers (i.e., pro-inflammatory cytokines and chemokine receptors) and alterations in connexin (Cxs) and pannexin (Panx) expression, likely responsible for dysregulation of the microglia/astrocyte network. Specifically, we found downregulation of Cx26 and Cx30 in the cochlea, and high level of Cx43 and Panx1 in the ACx.
CONCLUSIONS: Collectively, our results provide novel evidence on the role of immune and glial cell activation in the oxidative/inflammatory damage induced by
styrene in the auditory system at both peripheral and central levels, also involving alterations of gap junction networks. Our data suggest that targeting glial cells and connexin/pannexin expression might be useful to attenuate oxidative/inflammatory damage in the auditory system.