Effects of Chronic Spinal Cord Injury on Relationships among Ion Channel and Receptor mRNAs in Mouse Lumbar Spinal Cord
Effects of Chronic Spinal Cord Injury on Relationships among Ion Channel and Receptor mRNAs in Mouse Lumbar Spinal Cord
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DOI：
10.1016/j.neuroscience.2018.09.034
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发表时间：
2018-11-21
期刊：
影响因子：
3.3
通讯作者：
Schulz，David J.
中科院分区：
文献类型：
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作者：
Garcia，Virginia B.;Abbinanti，Matthew D.;Schulz，David J.
脊髓损伤（SCI）引起脊髓基因表达的广泛变化，即使在病变水平以下的未受损脊髓中也是如此。关于SCI后相关基因表达的变化知之甚少。我们研究了电压门控离子通道和神经递质受体mRNA水平之间的基因共表达网络，采用定量RT-PCR在对照组和慢性SCI动物的小鼠腰髓纵向切片。这些纵向切片从脊髓的腹侧表面制成，从而形成相对富含运动神经元或中间神经元的切片。我们对来自每个样品的50个离子通道或受体转录物的mRNA拷贝数进行绝对定量，并使用多重相关分析来检测所有基因对中相关mRNA水平的模式。大多数通道和受体的表达因慢性SCI而改变，但在切片水平上有所不同。此外，运动神经元富集切片经历了相关通道和受体表达的整体损失，而中间神经元切片显示出正相关转录本数量的急剧增加。这些相关性表明，脊髓损伤诱导不同类型的细胞在组织的离子通道和递质受体的基因共表达网络的不同变化。
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.