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首页> 外文期刊>GMS Current Posters in Otorhinolaryngology,Head and Neck Surgery >Determination of the apoptosis and cell survival signal transduction in the rat cochlea following neomycin induced deafness
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Determination of the apoptosis and cell survival signal transduction in the rat cochlea following neomycin induced deafness

机译:新霉素致聋后大鼠耳蜗细胞凋亡及细胞存活信号转导的测定

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Abstract Introduction: Sensorineural hearing loss is associated with loss of the hair cells in the cochlea. By the common hypothesis, cell death provoked by deafferentation of neurons may reflect deprivation of the neurotrophic factors. In this project signalling of neurotrophic factors in the context of apoptotic mechanisms in the auditory nerve (AN) by gene expression analysis following 7, 14, and 28 days deafening is determined. Methods: Differential gene expression of BDNF and GDNF, their receptors trkB, p75NTR and GFRα1, the pro-apoptotic signal molecules caspase 9, Bax and anti-apoptotic signal molecules GLAST, Bcl-2 are being studied within this time interval by real time-PCR. For that total RNA was extracted from the AN of 20 normal and deafened animal, respectively, sacrificed after 7 day. Morphometric analysis of the AN degeneration was immunhistologically determined by spiral ganglion neuron (SGN) serial counts. Confirmation of the deafening process in 7day group was done by auditory brainstem response. Results: Following the establishment of the housekeeping gene Rplp2 (ribosomal protein) as the internal standard we found an increase in the RNA level of GDNF and the receptors GFRα1, p75 and trkB demonstrating an early upregulation of neurotrophic factor. A significant 1.8 fold decrease of the SGN was demonstrated following 7 days deafening indicating strong apoptosis process. Conclusion: In general, gene expression data cannot be related to function, however, they allow the verification of the neurotrophin hypothesis. As well, gene expression profiling may clarify the role of neurotrophic factors in the deafening process within the time intervall of deafness.Supported by: Georg Christoph Lichtenberg Scholarship, Lower Saxony
机译:摘要简介:感觉神经性听力损失与耳蜗毛细胞的损失有关。根据普遍的假设,神经元脱细胞引起的细胞死亡可能反映了神经营养因子的丧失。在该项目中,通过耳聋后7天,14天和28天的基因表达分析,确定了在听神经(AN)凋亡机制中神经营养因子的信号传导。方法:在此时间间隔内,实时研究BDNF和GDNF的差异基因表达,其受体trkB,p75NTR和GFRα1,凋亡信号分子caspase 9,Bax和抗凋亡信号分子GLAST,Bcl-2。 PCR。为此,分别从20只正常和耳聋的动物的AN中提取总RNA,在7天后处死。通过螺旋神经节神经元(SGN)序列计数免疫组织学确定AN变性的形态分析。通过听性脑干反应来确认7天组的耳聋过程。结果:建立看家基因Rplp2(核糖体蛋白)作为内标后,我们发现GDNF的RNA水平升高,受体GFRα1,p75和trkB升高,表明神经营养因子的早期上调。耳聋7天后,SGN明显降低了1.8倍,表明细胞凋亡过程很强。结论:一般而言,基因表达数据与功能无关,但是它们可以验证神经营养蛋白的假说。同样,基因表达谱分析可以阐明神经营养因子在耳聋时间间隔内在耳聋过程中的作用。支持者:下萨克森州乔治·克里斯托夫·利希滕贝格奖学金

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