Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Exp Neurol. 2012 Jan;233(1):447-56. doi: 10.1016/j.expneurol.2011.11.018. Epub 2011 Nov 19.
We investigated microRNAs (miRs) associated with PTEN/mTOR signaling after spinal cord injury (SCI) and after hind limb exercise (Ex), a therapy implicated in promoting spinal cord plasticity. After spinalization, rats received cycling Ex 5 days/week. The expression of miRs, their target genes and downstream effectors were probed in spinal cord tissue at 10 and 31 days post injury. Ex elevated expression of miR21 and decreased expression of miR 199a-3p correlating with significant change in the expression of their respective target genes: PTEN mRNA decreased and mTOR mRNA increased. Western blotting confirmed comparable changes in protein levels. An increase in phosphorylated-S6 (a downstream effector of mTOR) within intermediate grey neurons in Ex rats was blocked by Rapamycin treatment. It thus appears possible that activity-dependent plasticity in the injured spinal cord is modulated in part through miRs that regulate PTEN and mTOR signaling and may indicate an increase in the regenerative potential of neurons affected by a SCI.
我们研究了脊髓损伤(SCI)后和下肢运动(Ex)后与 PTEN/mTOR 信号相关的 microRNAs(miRs),Ex 是一种被认为能促进脊髓可塑性的治疗方法。脊柱切断后,大鼠每周接受 5 天的循环 Ex。在损伤后 10 和 31 天,检测脊髓组织中 miRs、其靶基因和下游效应物的表达。Ex 上调了 miR21 的表达,下调了 miR199a-3p 的表达,与其各自靶基因的表达变化相关:PTEN mRNA 减少,mTOR mRNA 增加。Western blotting 证实了蛋白水平的相应变化。雷帕霉素处理阻断了 Ex 大鼠中间灰色神经元中磷酸化-S6(mTOR 的下游效应物)的增加。因此,受伤脊髓中的活动依赖性可塑性可能部分通过调节 PTEN 和 mTOR 信号的 miRs 来调节,这可能表明受 SCI 影响的神经元的再生潜力增加。