Regulatory effects of intermittent noxious stimulation on spinal cord injury-sensitive microRNAs and their presumptive targets following spinal cord contusion.
Regulatory effects of intermittent noxious stimulation on spinal cord injury-sensitive microRNAs and their presumptive targets following spinal cord contusion.
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DOI：
10.3389/fncir.2014.00117
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发表时间：
2014
影响因子：
3.5
通讯作者：
Miranda RC
中科院分区：
文献类型：
--
作者：
Strickland ER;Woller SA;Garraway SM;Hook MA;Grau JW;Miranda RC
不可控制的伤害性刺激对脊髓挫伤大鼠的恢复有不利影响。脊髓损伤（SCI）导致病变部位和病变部位远端的microRNA（miRNA）表达改变。我们假设，无法控制的伤害性感受进一步影响SCI敏感的miRNA和相关的基因靶点，可能解释适应不良可塑性的进展。我们的数据验证了先前描述的miRNAs对单独SCI的敏感性。此外，脊髓损伤后，间歇性伤害性刺激后24 h脊髓背侧的miR 124表达降低，7 d脊髓背侧的miR 129 -2和腹侧的miR 1表达增加。我们还发现，脑源性神经营养因子（BDNF）的mRNA表达显着下调后1天单独SCI，并显着更，SCI后，尾休克。胰岛素样生长因子-1（IGF-1）mRNA表达在SCI后1天和7天均显著增加，并且在SCI休克后7天显著增加。miR-1表达与IGF-1呈显著正相关，而与BDNF mRNA表达无相关性。进一步的逐步线性回归分析表明，BDNF和IGF-1 mRNA表达的变化的显着比例解释了两组miRNA的方差，这意味着共调节。总的来说，这些数据表明，激活损伤部位远端感觉运动回路的不可控制的伤害性感受影响损伤部位内的SCI-miRNA和靶mRNA。SCI敏感的miRNAs可能很好地介导了不受控制的感觉运动激活对功能恢复的不良后果。然而，它们对远端感觉输入的敏感性也暗示这些miRNA是SCI和神经性疼痛管理的候选靶点。
Uncontrollable nociceptive stimulation adversely affects recovery in spinally contused rats. Spinal cord injury (SCI) results in altered microRNA (miRNA) expression both at, and distal to the lesion site. We hypothesized that uncontrollable nociception further influences SCI-sensitive miRNAs and associated gene targets, potentially explaining the progression of maladaptive plasticity. Our data validated previously described sensitivity of miRNAs to SCI alone. Moreover, following SCI, intermittent noxious stimulation decreased expression of miR124 in dorsal spinal cord 24 h after stimulation and increased expression of miR129-2 in dorsal, and miR1 in ventral spinal cord at 7 days. We also found that brain-derived neurotrophic factor (BDNF) mRNA expression was significantly down-regulated 1 day after SCI alone, and significantly more so, after SCI followed by tailshock. Insulin-like growth factor-1 (IGF-1) mRNA expression was significantly increased at both 1 and 7 days post-SCI, and significantly more so, 7 days post-SCI with shock. MiR1 expression was positively and significantly correlated with IGF-1, but not BDNF mRNA expression. Further, stepwise linear regression analysis indicated that a significant proportion of the changes in BDNF and IGF-1 mRNA expression were explained by variance in two groups of miRNAs, implying co-regulation. Collectively, these data show that uncontrollable nociception which activates sensorimotor circuits distal to the injury site, influences SCI-miRNAs and target mRNAs within the lesion site. SCI-sensitive miRNAs may well mediate adverse consequences of uncontrolled sensorimotor activation on functional recovery. However, their sensitivity to distal sensory input also implicates these miRNAs as candidate targets for the management of SCI and neuropathic pain.
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SCI后的运动疗法和恢复：显示早期干预的证据改善了功能的恢复。
影响因子：
2.2
作者：
Brown, A. K.;Woller, S. A.;Moreno, G.;Grau, J. W.;Hook, M. A.
通讯作者：
Hook, M. A.
影响因子：
--
作者：
Boyce, Vanessa S;Mendell, Lorne M
通讯作者：
Mendell, Lorne M
影响因子：
2.9
作者：
Crown, ED;Ferguson, AR;Grau, JW
通讯作者：
Grau, JW
脊髓挫伤损伤后，间歇性有害刺激会损害运动的恢复，并减少脊柱脑源性的神经营养因子 - 霉菌素 - 肌球蛋白受体激素激酶信号传导。
影响因子：
3.3
作者：
Garraway, S. M.;Turtle, J. D.;Huie, J. R.;Lee, K. H.;Hook, M. A.;Woller, S. A.;Grau, J. W.
通讯作者：
Grau, J. W.
影响因子：
3.4
作者：
Garraway, SM;Petruska, JC;Mendell, LM
通讯作者：
Mendell, LM