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声学刺激改变了大鼠耳蜗螺旋神经节神经元中基质细胞衍生因子-1 的表达。

Acoustical stimulus changes the expression of stromal cell-derived factor-1 in the spiral ganglion neurons of the rat cochlea.

机构信息

Ji-Guan Hospital, Lanzhou Military Region, Air Force, PLA, Lanzhou 730020, China; Department of Otolaryngology-Head and Neck Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.

Department of Aerospace Biodynamics, Faculty of Aerospace Medicine, Fourth Military Medical University, Xi'an 710032, China.

出版信息

Neurosci Lett. 2014 Feb 21;561:140-5. doi: 10.1016/j.neulet.2013.12.061. Epub 2014 Jan 3.

Abstract

Neural stem cell (NSC) transplantation into the cochlea has been tested as a treatment for spiral ganglion neuron (SGN) degenerative disease and injury in various animal models. A recent study has shown evidence of functional recovery after transplantation of the stem cells into a degenerated-SGN model. Chemokine stromal cell-derived factor-1 (SDF-1, or known as CXC chemokine ligand-12, CXCL-12) signaling through CXCR4 has previously been identified as a key step in the homing of the stem cells within the injury areas; meanwhile, studies have revealed that the SDF-1/CXCR4 axis is also involved in axon guidance and pathfinding. A study found that transplanted neural precursor cells can migrate to the root of the auditory nerve when animals are subjected to an augmented acoustic environment (AAE). In accordance with these studies, we hypothesize that AAE will up-regulate the expression of SDF-1 in acoustic nerves. We tested our hypothesis by examining the expression of SDF-1 in different acoustic environments, and the results were confirmed by the auditory brainstem response (ABR), immunohistochemical and RT-PCR analyses. The results showed that SDF-1 was expressed at a relatively low level in the SGNs under normal animal unit acoustic conditions (40-50 dB). Moreover, it was significantly up-regulated in the SGNs under the 75 dB (augmented physiological process without hearing loss) and 90 dB AAE (pathological process with light hearing loss) conditions; however, under the 115 dB AAE (pathological process with severe hearing loss) condition, the expression of SDF-1 was not up-regulated. The results confirmed that appropriately augmented acoustical stimuli lead to the up-regulation of SDF-1, which may assist in the migration of the transplanted cells and the subsequent establishment of essential synaptic contacts between the exogenous cells and the host auditory pathway.

摘要

神经干细胞(NSC)移植到耳蜗已被测试为治疗螺旋神经节神经元(SGN)退行性疾病和损伤的一种方法,在各种动物模型中都有尝试。最近的一项研究表明,在退行性 SGN 模型中移植干细胞后,有功能恢复的证据。趋化因子基质细胞衍生因子-1(SDF-1,也称为 CXC 趋化因子配体-12,CXCL-12)通过 CXCR4 的信号传递以前被确定为干细胞在损伤区域内归巢的关键步骤;同时,研究表明 SDF-1/CXCR4 轴也参与轴突导向和寻径。一项研究发现,当动物处于增强的声环境(AAE)中时,移植的神经前体细胞可以迁移到听神经的根部。根据这些研究,我们假设 AAE 将上调听神经中 SDF-1 的表达。我们通过检查不同声环境中 SDF-1 的表达来检验我们的假设,结果通过听觉脑干反应(ABR)、免疫组织化学和 RT-PCR 分析得到证实。结果表明,在正常动物单位声条件(40-50dB)下,SDF-1 在 SGN 中的表达水平相对较低。此外,在 75dB(增强的生理过程,无听力损失)和 90dB AAE(轻度听力损失的病理过程)条件下,SDF-1 在 SGN 中的表达显著上调;然而,在 115dB AAE(严重听力损失的病理过程)条件下,SDF-1 的表达没有上调。结果证实,适当增强的声刺激导致 SDF-1 的上调,这可能有助于移植细胞的迁移以及外源性细胞与宿主听觉通路之间随后建立必要的突触联系。

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