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Combined exposure to carbon disulfide and low-frequency noise reversibly affects vestibular function
NeuroToxicology ( IF 3.4 ) Pub Date : 2018-06-19 , DOI: 10.1016/j.neuro.2018.06.010
Monique Chalansonnet , Maria Carreres-Pons , Thomas Venet , Aurélie Thomas , Lise Merlen , Carole Seidel , Frédéric Cosnier , Hervé Nunge , Benoît Pouyatos , Jordi Llorens , Pierre Campo

Chronic occupational exposure to carbon disulfide (CS2) has debilitating motor and sensory effects in humans, which can increase the risk of falls. Although no mention of vestibulotoxic effects is contained in the literature, epidemiological and experimental data suggest that CS2 could cause low-frequency hearing loss when associated with noise exposure. Low-frequency noise might also perturb the peripheral balance receptor through an as-yet unclear mechanism. Here, we studied how exposure to a low-frequency noise combined with 250-ppm CS2 affected balance in rats. Vestibular function was tested based on post-rotary nystagmus recorded by a video-oculography system. These measurements were completed by behavioral tests and analysis of the cerebellum to measure expression levels for gene expression associated with neurotoxicity. Assays were performed prior to and following a 4-week exposure, and again after a 4-week recovery period. Functional measurements were completed by histological analyses of the peripheral organs.Nystagmus was unaltered by exposure to noise alone, while CS2 alone caused a moderate 19% decrease of the saccade number. In contrast, coexposure to 250-ppm CS2 and low-frequency noise decreased both saccade number and duration by 33% and 34%, respectively. After four weeks, recovery was only partial but measures were not significantly different from pre-exposure values. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis of cerebellar tissue revealed a slight but significant modification in expression levels for two genes linked to neurotoxicity in CS2-exposed animals. However, neither histopathological changes to the peripheral receptor nor behavioral differences were observed. Based on all these results, we propose that the effects of CS2 were due to reversible neurochemical disturbance of the efferent pathways managing post-rotatory nystagmus. Because the nervous structures involving the vestibular function appear particularly sensitive to CS2, post-rotary nystagmus could be used as an early, non-invasive measurement to diagnose CS2 intoxication as part of an occupational conservation program.



中文翻译:

暴露于二硫化碳和低频噪声的组合可逆地影响前庭功能

长期职业性暴露于二硫化碳(CS2)对人体的运动和感觉有破坏作用,可增加跌倒的风险。尽管文献中没有提及前庭毒作用,但流行病学和实验数据表明,当与噪声接触时,CS2可能会导致低频听力损失。低频噪声还可能通过尚不清楚的机制干扰周围的平衡受体。在这里,我们研究了低频噪声与250 ppm CS2的结合如何影响大鼠的平衡。基于由视频眼动系统记录的旋转后眼球震颤来测试前庭功能。这些测量通过行为测试和小脑分析完成,以测量与神经毒性相关的基因表达的表达水平。在暴露4周之前和之后以及在恢复4周之后再次进行测定。通过对周围器官的组织学分析来完成功能性测量。眼球震颤不会因单独暴露于噪音而改变,而单独的CS2会使眼球扫视次数减少19%。相反,共同暴露于250 ppm CS2和低频噪声会使扫视次数和持续时间分别减少33%和34%。四周后,恢复只是部分,但测量值与接触前的值没有显着差异。小脑组织的实时定量聚合酶链反应(RT-qPCR)分析显示,暴露于CS2的动物中与神经毒性相关的两个基因的表达水平有轻微但明显的改变。然而,既未观察到外周受体的组织病理学变化,也未观察到行为差异。基于所有这些结果,我们认为CS2的影响是由于处理旋转后眼球震颤的传出途径的可逆神经化学紊乱引起的。由于涉及前庭功能的神经结构似乎对CS2尤其敏感,因此作为职业保护计划的一部分,旋转后眼球震颤可用作早期非侵入性测量来诊断CS2中毒。

更新日期:2018-06-19
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