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首页> 外文期刊>BMC Neuroscience >Long descending cervical propriospinal neurons differ from thoracic propriospinal neurons in response to low thoracic spinal injury
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Long descending cervical propriospinal neurons differ from thoracic propriospinal neurons in response to low thoracic spinal injury

机译：长期下降的颈椎脊髓神经元与胸椎脊髓神经元的区别在于对低胸椎损伤的反应

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Background Propriospinal neurons, with axonal projections intrinsic to the spinal cord, have shown a greater regenerative response than supraspinal neurons after axotomy due to spinal cord injury (SCI). Our previous work focused on the response of axotomized short thoracic propriospinal (TPS) neurons following a low thoracic SCI (T9 spinal transection or moderate spinal contusion injury) in the rat. The present investigation analyzes the intrinsic response of cervical propriospinal neurons having long descending axons which project into the lumbosacral enlargement, long descending propriospinal tract (LDPT) axons. These neurons also were axotomized by T9 spinal injury in the same animals used in our previous study. Results Utilizing laser microdissection (LMD), qRT-PCR, and immunohistochemistry, we studied LDPT neurons (located in the C5-C6 spinal segments) between 3-days, and 1-month following a low thoracic (T9) spinal cord injury. We examined the response of 89 genes related to growth factors, cell surface receptors, apoptosis, axonal regeneration, and neuroprotection/cell survival. We found a strong and significant down-regulation of ~25% of the genes analyzed early after injury (3-days post-injury) with a sustained down-regulation in most instances. In the few genes that were up-regulated (Actb, Atf3, Frs2, Hspb1, Nrap, Stat1) post-axotomy, the expression for all but one was down-regulated by 2-weeks post-injury. We also compared the uninjured TPS control neurons to the uninjured LDPT neurons used in this experiment for phenotypic differences between these two subpopulations of propriospinal neurons. We found significant differences in expression in 37 of the 84 genes examined between these two subpopulations of propriospinal neurons with LDPT neurons exhibiting a significantly higher base line expression for all but 3 of these genes compared to TPS neurons. Conclusions Taken collectively these data indicate a broad overall down-regulation in the genes examined, including genes for neurotrophic/growth factor receptors as well as for several growth factors. There was a lack of a significant regenerative response, with the exception of an up-regulation of Atf3 and early up-regulation of Hspb1 (Hsp27), both involved in cell stresseuroprotection as well as axonal regeneration. There was no indication of a cell death response over the first month post-injury. In addition, there appear to be significant phenotypic differences between uninjured TPS and LDPT neurons, which may partly account for the differences observed in their post-axotomy responses. The findings in this current study stand in stark contrast to the findings from our previous work on TPS neurons. This suggests that different approaches will be needed to enhance the capacity for each population of propriospinal neuron to survive and undergo successful axonal regeneration after SCI.
机译：背景由于脊髓损伤（SCI），轴突切除后的脊髓前突神经元比脊髓上神经元显示出更大的再生反应。我们以前的工作集中于在大鼠中出现低胸腔脊髓损伤（T9脊髓横断或中度脊髓挫伤性损伤）后，切除无胸廓的短脊椎脊髓（TPS）神经元的反应。本研究分析了具有长下降轴突的颈椎脊髓神经元的内在反应，该神经突突伸入腰s部增大，长下降脊索道（LDPT）轴突。在我们以前的研究中使用的相同动物中，这些神经元也被T9脊髓损伤轴突切除。结果利用激光显微解剖（LMD），qRT-PCR和免疫组织化学，我们研究了低胸（T9）脊髓损伤后3天至1个月之间的LDPT神经元（位于C5-C6脊髓节段）。我们检查了与生长因子，细胞表面受体，细胞凋亡，轴突再生和神经保护/细胞存活有关的89个基因的反应。我们发现，在受伤后早期（受伤后3天）分析的基因有25％的强烈而显着的下调，在大多数情况下，这些基因持续下调。在轴突切开后少数被上调的基因（Actb，Atf3，Frs2，Hspb1，Nrap，Stat1）中，除一个基因外，其余所有基因的表达在受伤后两周均被下调。我们还比较了未受伤的TPS对照神经元与本实验中使用的未受伤的LDPT神经元，以比较这两个脊椎神经元亚群之间的表型差异。我们发现，在这两个脊椎神经元亚群中，与LDPT神经元相比，除了TPS神经元之外，所有这些基因中的3个基因均表现出明显更高的基线表达，在这84个基因中，有37个基因在37个基因表达中存在显着差异。结论综上所述，这些数据表明所检查基因的总体总体下调，包括神经营养/生长因子受体的基因以及几种生长因子的基因。除了Atf3的上调和Hspb1（Hsp27）的早期上调外，都没有明显的再生反应，这两者都参与细胞应激/神经保护以及轴突再生。受伤后第一个月没有细胞死亡反应的迹象。此外，未受伤的TPS和LDPT神经元之间似乎存在显着的表型差异，这可能部分解释了其在轴突切除后反应中观察到的差异。这项当前研究的发现与我们以前在TPS神经元研究中的发现形成鲜明对比。这表明将需要不同的方法来增强SCI后每个脊椎神经元群体生存和成功进行轴突再生的能力。

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