Gene Transcript Alterations in the Spinal Cord, Anterior Cingulate Cortex, and Amygdala in Mice Following Peripheral Nerve Injury.
Gene Transcript Alterations in the Spinal Cord, Anterior Cingulate Cortex, and Amygdala in Mice Following Peripheral Nerve Injury.
复制标题
DOI：
10.3389/fcell.2021.634810
复制
发表时间：
2021
影响因子：
5.5
通讯作者：
Zang W
中科院分区：
文献类型：
--
作者：
Su S;Li M;Wu D;Cao J;Ren X;Tao YX;Zang W
由神经损伤引起的慢性神经性疼痛是最常见的临床症状，通常伴有焦虑和抑郁样症状。目前的治疗是非常有限的，至少部分是由于不完全理解这种疾病的机制。背根神经节（DRG）基因表达的变化已被公认为与神经病理性疼痛的发生有关，但周围神经损伤如何改变其他疼痛相关区域的基因表达仍不清楚。本研究采用更高测序深度的链特异性新一代RNA测序技术，观察单侧第四腰脊神经结扎（SNL）后脊髓（SC）、前扣带皮层（ACC）和杏仁核（AMY）全基因组转录物的变化。除了提供新的长非编码RNA（lncRNA）和mRNA的转录组谱外，我们还鉴定了疼痛和情绪相关的差异表达基因（DEG），并揭示了这些DEG的数量与神经炎症和细胞凋亡高度相关。功能分析表明，上调的mRNA主要参与免疫系统过程、细胞凋亡过程、防御反应、炎症反应和痛觉感知。此外，比较疼痛，焦虑和抑郁相关的DEG在三个区域之间呈现脊髓和脊髓上结构之间的特定分子图谱，并指示神经损伤后基因表达的区域依赖性和区域独立性改变。我们的研究为周围神经损伤后三个不同疼痛相关区域的基因转录表达模式提供了一个资源。我们的研究结果表明，神经炎症和细胞凋亡是神经病理性疼痛的重要致病机制，一些DEG可能是有前途的治疗靶点。
Chronic neuropathic pain caused by nerve damage is a most common clinical symptom, often accompanied by anxiety- and depression-like symptoms. Current treatments are very limited at least in part due to incompletely understanding mechanisms underlying this disorder. Changes in gene expression in the dorsal root ganglion (DRG) have been acknowledged to implicate in neuropathic pain genesis, but how peripheral nerve injury alters the gene expression in other pain-associated regions remains elusive. The present study carried out strand-specific next-generation RNA sequencing with a higher sequencing depth and observed the changes in whole transcriptomes in the spinal cord (SC), anterior cingulate cortex (ACC), and amygdala (AMY) following unilateral fourth lumbar spinal nerve ligation (SNL). In addition to providing novel transcriptome profiles of long non-coding RNAs (lncRNAs) and mRNAs, we identified pain- and emotion-related differentially expressed genes (DEGs) and revealed that numbers of these DEGs displayed a high correlation to neuroinflammation and apoptosis. Consistently, functional analyses showed that the most significant enriched biological processes of the upregulated mRNAs were involved in the immune system process, apoptotic process, defense response, inflammation response, and sensory perception of pain across three regions. Moreover, the comparisons of pain-, anxiety-, and depression-related DEGs among three regions present a particular molecular map among the spinal cord and supraspinal structures and indicate the region-dependent and region-independent alterations of gene expression after nerve injury. Our study provides a resource for gene transcript expression patterns in three distinct pain-related regions after peripheral nerve injury. Our findings suggest that neuroinflammation and apoptosis are important pathogenic mechanisms underlying neuropathic pain and that some DEGs might be promising therapeutic targets.
登录
查看更多内容
影响因子：
3
作者：
Gangarossa G;Laffray S;Bourinet E;Valjent E
通讯作者：
Valjent E
影响因子：
6.2
作者：
Chandley MJ;Crawford JD;Szebeni A;Szebeni K;Ordway GA
通讯作者：
Ordway GA
影响因子：
7.4
作者：
Bushnell MC;Case LK;Ceko M;Cotton VA;Gracely JL;Low LA;Pitcher MH;Villemure C
通讯作者：
Villemure C
影响因子：
3.6
作者：
Darvish-Ghane, Soroush;Quintana, Clementine;Martin, Loren J.
通讯作者：
Martin, Loren J.
影响因子：
81.5
作者：
Colloca, Luana;Ludman, Taylor;Raja, Srinivasa N.
通讯作者：
Raja, Srinivasa N.