Exposure to acoustic stimuli promotes the development and differentiation of neural stem cells from the cochlear nuclei through the clusterin pathway.

Exposure to acoustic stimuli promotes the development and differentiation of neural stem cells from the cochlear nuclei through the clusterin pathway.
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暴露于声刺激可通过聚集蛋白途径促进耳蜗核神经干细胞的发育和分化

DOI:
10.3892/ijmm.2015.2075
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发表时间:
2015-03
影响因子:
5.4
通讯作者:
Qiu JH
Qiu JH
中科院分区:
医学3区
文献类型:
--
作者:
Xue T;Wei L;Zha DJ;Qiao L;Lu LJ;Chen FQ;Qiu JH

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干细胞治疗已经引起了广泛关注的一些疾病。近年来,耳蜗核神经干细胞的发现为感音神经性耳聋的治疗指明了一个潜在的方向。声刺激在听觉系统的发育中起着重要的作用。在这项研究中,我们的目的是确定是否声刺激诱导神经干细胞的发展和分化,通过上调clusterin(CLU)在神经干细胞分离耳蜗核。为了进一步阐明声刺激下神经干细胞发育和分化的机制,我们成功构建了CLU沉默的动物模型。正如预期的那样,来自用LV-CLU shRNA处理的大鼠的NSC在暴露于增强的声学环境(AAE)时表现出较低的增殖率。此外,CLU基因表达沉默后,AAE诱导的细胞凋亡抑制作用消失。在声刺激暴露的干细胞分化为神经元的过程中,星形胶质细胞的数量显着减少,证明了细胞标志物,微管相关蛋白-2(MAP-2)和胶质细胞酸性蛋白(GFAP)的表达,这是显着抑制时,CLU基因被沉默。本研究结果表明,声刺激可能主要通过CLU通路诱导耳蜗神经干细胞的发育和分化。我们的研究表明,CLU可能是治疗感音神经性听力损失的新靶点。
Stem cell therapy has attracted widespread attention for a number of diseases. Recently, neural stem cells (NSCs) from the cochlear nuclei have been identified, indicating a potential direction for the treatment of sensorineural hearing loss. Acoustic stimuli play an important role in the development of the auditory system. In this study, we aimed to determine whether acoustic stimuli induce NSC development and differentiation through the upregulation of clusterin (CLU) in NSCs isolated from the cochlear nuclei. To further clarify the underlying mechanisms involved in the development and differentiation of NSCs exposed to acoustic stimuli, we successfully constructed animal models in which was CLU silenced by an intraperitoneal injection of shRNA targeting CLI. As expected, the NSCs from rats treated with LV-CLU shRNA exhibited a lower proliferation ratio when exposed to an augmented acoustic environment (AAE). Furthermore, the inhibition of cell apoptosis induced by exposure to AAE was abrogated after silencing the expression of the CLU gene. During the differentiation of acoustic stimuli-exposed stem cells into neurons, the number of astrocytes was significantly reduced, as evidenced by the expression of the cell markers, microtubule associated protein-2 (MAP-2) and glial fibrillary acidic protein (GFAP), which was markedly inhibited when the CLU gene was silenced. Our results indicate that acoustic stimuli may induce the development and differentiation of NSCs from the cochlear nucleus mainly through the CLU pathway. Our study suggests that CLU may be a novel target for the treatment of sensorineural hearing loss.
DOI: 10.1016/j.cell.2009.02.013
发表时间: 2009-03-06
期刊: Cell
影响因子: 64.5
作者:
Soldner F;Hockemeyer D;Beard C;Gao Q;Bell GW;Cook EG;Hargus G;Blak A;Cooper O;Mitalipova M;Isacson O;Jaenisch R
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发表时间: 2007-06-01
期刊: HEARING RESEARCH
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发表时间: 2001-08-01
影响因子: 15.9
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DOI: 10.1038/nm925
发表时间: 2003-10-01
期刊: NATURE MEDICINE
影响因子: 82.9
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DOI: 10.1016/0896-6273(94)90046-9
发表时间: 1994-11-01
期刊: NEURON
影响因子: 16.2
作者:
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