Differential gene expression changes in the dorsal root versus trigeminal ganglia following peripheral nerve injury in rats
Differential gene expression changes in the dorsal root versus trigeminal ganglia following peripheral nerve injury in rats
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DOI：
10.1002/ejp.1546
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发表时间：
2020-05-01
影响因子：
3.6
通讯作者：
Benoliel, Rafael
中科院分区：
文献类型：
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作者：
Korczeniewska, Olga A.;Rider, Giannina Katzmann;Benoliel, Rafael
背根神经节（DRG）和三叉神经节（TG）分别含有脊髓和三叉神经系统感觉神经元的胞体。它们是彼此的同源物;然而，这两个系统对损伤的反应存在差异。三叉神经损伤很少导致慢性神经性疼痛（NP）。到目前为止，还没有发现涉及两个系统之间对神经损伤的差异反应的基因。我们研究了转录的变化参与三叉神经和脊髓NP的发展。方法三叉神经和脊髓单神经病变引起的慢性压迫性损伤眶下或坐骨神经。采用实时荧光定量PCR技术检测伤后4、8、21 d时TG和DRG中84个基因的表达水平。结果我们发现TG和DRG中存在时间依赖性和神经节特异性的转录调控，这可能与相应神经病变的发生发展有关。伤后4d，在两个神经节中表达显著的基因中，Cnr 2、Grm 5、Htr 1a、Il 10、Oprd 1、Pdyn、Prok 2和Tacr 1在TG中表达上调，在DRG中表达下调;伤后21天，Adora 1、Cd 200、Comt、Maob、Mapk 3、P2 rx 4、Ptger 1、TNF和Slc 6a 2在TG中显著上调，但在DRG中下调。结论我们的研究结果表明，由于创伤引起的脊髓和三叉神经病变的差异调节。微妙的，但重要的两个神经节之间的差异可能会影响NP development.Significance我们提出了不同的转录改变在TG和DRG中，可能有助于观察到相应的mononeuropathies的差异。由于三叉神经系统似乎对创伤后发生NP更有抵抗力，我们的研究结果为未来的研究奠定了基础，以检测可能以保护或促进方式发挥作用的基因和途径。这些可能是新的和重要的治疗靶点。
Background The dorsal root (DRG) and trigeminal (TG) ganglia contain cell bodies of sensory neurons of spinal and trigeminal systems, respectively. They are homologs of each other; however, differences in how the two systems respond to injury exist. Trigeminal nerve injuries rarely result in chronic neuropathic pain (NP). To date, no genes involved in the differential response to nerve injury between the two systems have been identified. We examined transcriptional changes involved in the development of trigeminal and spinal NP.Methods Trigeminal and spinal mononueropathies were induced by chronic constriction injury to the infraorbital or sciatic nerve. Expression levels of 84 genes in the TG and DRG at 4, 8 and 21 days post-injury were measured using real-time PCR.Results We found time-dependent and ganglion-specific transcriptional regulation that may contribute to the development of corresponding neuropathies. Among genes significantly regulated in both ganglia Cnr2, Grm5, Htr1a, Il10, Oprd1, Pdyn, Prok2 and Tacr1 were up-regulated in the TG but down-regulated in the DRG at 4 days post-injury; at 21 days post-injury, Adora1, Cd200, Comt, Maob, Mapk3, P2rx4, Ptger1, Tnf and Slc6a2 were significantly up-regulated in the TG but down-regulated in the DRG.Conclusions Our findings suggest that spinal and trigeminal neuropathies due to trauma are differentially regulated. Subtle but important differences between the two ganglia may affect NP development.Significance We present distinct transcriptional alterations in the TG and DRG that may contribute to differences observed in the corresponding mononeuropathies. Since the trigeminal system seems more resistant to developing NP following trauma our findings lay ground for future research to detect genes and pathways that may act in a protective or facilitatory manner. These may be novel and important therapeutic targets.