背景:背根神经节(DRG)神经元来自神经c,主要支配皮肤,颈状结节复合体(JNC)神经元起源于胎盘和神经支配的内部器官。这些神经节由旨在评估和保持体内平衡的高度异质的神经元组组成。在其他亚型中,伤害性感受器神经元专门用于感知和响应环境危险。由于形式通常遵循功能,我们假设JNC和DRG神经元在表型和转录上不同。
方法:离体培养小鼠JNC和DRG神经元。使用钙成像,qPCR和神经突生长测定,我们比较了JNC和DRG神经元的敏感性。使用现有RNA测序数据集的计算机模拟分析,我们将我们的结果与两个神经节之间发现的转录组差异相对应。
结果:我们发现瞬时受体电位(TRP)通道的表达水平截然不同,JNC和DRG神经元中的生长因子受体和神经肽。功能上,幼稚JNC神经元TRP通道比DRG神经元对热信号更敏感。然而,DRG神经元显示TRP通道反应性增加,当暴露于神经生长因子(NGF)时,神经肽释放和神经突生长。相比之下,JNC神经元优先响应脑源性神经营养因子(BDNF)。
结论:我们的数据表明JNC和DRG神经元在转录和功能上是独特的,并且疼痛敏感性在解剖部位不同。靶向NGF信号传导的药物可能具有治疗内脏痛的有限功效。生物电子学神经刺激也应根据被靶向的神经节及其不同的表达谱进行调整。
BACKGROUND: Dorsal Root Ganglia (DRG) neurons are derived from the neural crest and mainly innervate the skin, while Jugular Nodose Complex (JNC) neurons originate from the placode and innervate internal organs. These ganglia are composed of highly heterogeneous groups of neurons aimed at assessing and preserving homeostasis. Among other subtypes, nociceptor neurons are specialized in sensing and responding to environmental dangers. As form typically follows function, we hypothesized that JNC and DRG neurons would be phenotypically and transcriptomically different.
METHODS: Mouse JNC and DRG neurons were cultured ex vivo. Using calcium imaging, qPCR and neurite outgrowth assay, we compared the sensitivity of JNC and DRG neurons. Using in-silico analysis of existing RNA sequencing datasets, we confronted our results to transcriptomic differences found between both ganglia.
RESULTS: We found drastically different expression levels of Transient Receptor Potential (TRP) channels, growth factor receptors and neuropeptides in JNC and DRG neurons. Functionally, naïve JNC neurons\' TRP channels are more sensitive to thermal cues than the ones from DRG neurons. However, DRG neurons showed increased TRP channel responsiveness, neuropeptide release and neurite outgrowth when exposed to Nerve Growth Factor (NGF). In contrast, JNC neurons preferentially responded to Brain-derived neurotrophic factor (BDNF).
CONCLUSIONS: Our data show that JNC and DRG neurons are transcriptomically and functionally unique and that pain sensitivity is different across anatomical sites. Drugs targeting NGF signaling may have limited efficacy to treat visceral pain. Bioelectronics nerve stimulation should also be adjusted to the ganglia being targeted and their different expression profile.