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背根损伤后大鼠和人初级感觉神经元中信号素、神经纤毛蛋白、血管内皮生长因子和腱生蛋白的表达

Expression of Semaphorins, Neuropilins, VEGF, and Tenascins in Rat and Human Primary Sensory Neurons after a Dorsal Root Injury.

作者信息

Lindholm Tomas, Risling Mårten, Carlstedt Thomas, Hammarberg Henrik, Wallquist Wilhelm, Cullheim Staffan, Sköld Mattias K

机构信息

Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden; Helsa Företagshälsovård Östermalm, Stockholm, Sweden.

Department of Neuroscience, Karolinska Institutet , Stockholm , Sweden.

出版信息

Front Neurol. 2017 Feb 21;8:49. doi: 10.3389/fneur.2017.00049. eCollection 2017.

Abstract

Dorsal root injury is a situation not expected to be followed by a strong regenerative growth, or growth of the injured axon into the central nervous system of the spinal cord, if the central axon of the dorsal root is injured but of strong regeneration if subjected to injury to the peripherally projecting axons. The clinical consequence of axonal injury is loss of sensation and may also lead to neuropathic pain. In this study, we have used hybridization to examine the distribution of mRNAs for the neural guidance molecules semaphorin 3A (SEMA3A), semaphorin 3F (SEMA3F), and semaphorin 4F (SEMA4F), their receptors neuropilin 1 (NP1) and neuropilin 2 (NP2) but also for the neuropilin ligand vascular endothelial growth factor (VEGF) and Tenascin J1, an extracellular matrix molecule involved in axonal guidance, in rat dorsal root ganglia (DRG) after a unilateral dorsal rhizotomy (DRT) or sciatic nerve transcetion (SNT). The studied survival times were 1-365 days. The different forms of mRNAs were unevenly distributed between the different size classes of sensory nerve cells. The results show that mRNA for SEMA3A was diminished after trauma to the sensory nerve roots in rats. The SEMA3A receptor NP1, and SEMA3F receptor NP2, was significantly upregulated in the DRG neurons after DRT and SNT. SEMA4F was upregulated after a SNT. The expression of mRNA for VEGF in DRG neurons after DRT showed a significant upregulation that was high even a year after the injuries. These data suggest a role for the semaphorins, neuropilins, VEGF, and J1 in the reactions after dorsal root lesions.

摘要

背根损伤是一种预期不会伴随强烈再生性生长的情况,即如果背根的中枢轴突受损,受损轴突不会向脊髓的中枢神经系统生长,但如果外周投射轴突受到损伤则会有强烈的再生。轴突损伤的临床后果是感觉丧失,还可能导致神经性疼痛。在本研究中,我们使用杂交技术来检测神经导向分子信号素3A(SEMA3A)、信号素3F(SEMA3F)和信号素4F(SEMA4F)、它们的受体神经纤毛蛋白1(NP1)和神经纤毛蛋白2(NP2),以及神经纤毛蛋白配体血管内皮生长因子(VEGF)和腱生蛋白J1(一种参与轴突导向的细胞外基质分子)在大鼠背根神经节(DRG)中的mRNA分布,这些大鼠经历了单侧背根切断术(DRT)或坐骨神经横断术(SNT)。研究的存活时间为1至365天。不同形式的mRNA在不同大小类别的感觉神经细胞中分布不均。结果表明,大鼠感觉神经根损伤后,SEMA3A的mRNA减少。DRT和SNT后,DRG神经元中SEMA3A受体NP1和SEMA3F受体NP2显著上调。SNT后SEMA4F上调。DRT后DRG神经元中VEGF的mRNA表达显著上调,即使在损伤一年后仍很高。这些数据表明信号素、神经纤毛蛋白、VEGF和J1在背根损伤后的反应中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bdf/5318460/38c2ff56caf3/fneur-08-00049-g001.jpg

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