Division of Biological Sciences, University of Missouri, Columbia, MO 65211, USA.
Department of Neurobiology and Behavior, Cornell University, Ithaca NY 14853, USA.
Neuroscience. 2018 Nov 21;393:42-60. doi: 10.1016/j.neuroscience.2018.09.034. Epub 2018 Sep 30.
Spinal cord injury (SCI) causes widespread changes in gene expression of the spinal cord, even in the undamaged spinal cord below the level of the lesion. Less is known about changes in the correlated expression of genes after SCI. We investigated gene co-expression networks among voltage-gated ion channel and neurotransmitter receptor mRNA levels using quantitative RT-PCR in longitudinal slices of the mouse lumbar spinal cord in control and chronic SCI animals. These longitudinal slices were made from the ventral surface of the cord, thus forming slices relatively enriched in motor neurons or interneurons. We performed absolute quantitation of mRNA copy number for 50 ion channel or receptor transcripts from each sample, and used multiple correlation analyses to detect patterns in correlated mRNA levels across all pairs of genes. The majority of channels and receptors changed in expression as a result of chronic SCI, but did so differently across slice levels. Furthermore, motor neuron-enriched slices experienced an overall loss of correlated channel and receptor expression, while interneuron slices showed a dramatic increase in the number of positively correlated transcripts. These correlation profiles suggest that spinal cord injury induces distinct changes across cell types in the organization of gene co-expression networks for ion channels and transmitter receptors.
脊髓损伤 (SCI) 导致脊髓内广泛的基因表达变化,即使在损伤水平以下的未受损脊髓中也是如此。关于 SCI 后相关基因表达变化的了解较少。我们使用定量 RT-PCR 研究了电压门控离子通道和神经递质受体 mRNA 水平在慢性 SCI 动物和对照动物的小鼠腰椎脊髓的纵向切片中的基因共表达网络。这些纵向切片是从脊髓的腹面制作的,因此形成了相对富含运动神经元或中间神经元的切片。我们对每个样本的 50 个离子通道或受体转录本的 mRNA 拷贝数进行了绝对定量,并使用多元相关分析来检测所有基因对之间相关 mRNA 水平的模式。大多数通道和受体因慢性 SCI 而改变表达,但在切片水平上的变化方式不同。此外,富含运动神经元的切片经历了相关通道和受体表达的整体丧失,而中间神经元切片中阳性相关转录本的数量显著增加。这些相关谱表明,脊髓损伤导致离子通道和递质受体基因共表达网络的组织在细胞类型上发生了不同的变化。