Quantitative Characterization of the Neuropeptide Level Changes in Dorsal Horn and Dorsal Root Ganglia Regions of the Murine Itch Models.
Quantitative Characterization of the Neuropeptide Level Changes in Dorsal Horn and Dorsal Root Ganglia Regions of the Murine Itch Models.
复制标题
小鼠瘙痒模型背角和背根神经节区域神经肽水平变化的定量表征。
DOI：
10.1021/acs.jproteome.9b00758
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发表时间：
2020
影响因子：
4.4
通讯作者：
Sweedler,JonathanV
中科院分区：
文献类型：
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作者：
Tillmaand,EmilyG;Anapindi,KrishnaDB;DeLaToba,EduardoA;Guo,ChangxiongJ;Krebs,Jessica;Lenhart,AshleyE;Liu,Qin;Sweedler,JonathanV
慢性瘙痒可能是极具破坏性的，在许多情况下，难以治疗。治疗瘙痒障碍的一个挑战是对参与从外周神经系统到中枢神经系统的瘙痒感觉交流的众多化学参与者的了解有限。神经肽是一种细胞间信号分子，参与将瘙痒信号从初级传入神经元（检测皮肤中的瘙痒）传递到脊髓和大脑的高阶回路。为了研究神经肽在传递瘙痒信号中的作用，我们建立了两种慢性瘙痒小鼠模型-丙酮-醚-水（AEW，皮肤干燥）和钙化三醇（MC903，特应性皮炎）。为了鉴定和定量多肽，我们使用液相色谱-串联质谱法分析了慢性瘙痒小鼠背根神经节（DRG）和背角（DH）组织的多肽含量。在数据库检索的辅助下，DH MC903有335个多肽，DH AEW有318个多肽，DRG MC903有266个多肽，DRG AEW有271个多肽。在这些可量化的多肽中，经过多次测试校正（q≤0.1），我们检测到30个在测试模型中受到差异调节。这些包括从神经肽前体衍生的几种候选肽，如proSAAS、proachykinin -1、proenkephalin和降钙素基因相关肽，其中一些先前与瘙痒有关。在这项研究中鉴定的肽可能有助于阐明我们对这些衰弱性疾病的理解。数据可通过ProteomeXchange获得，标识符为PXD015949。
Chronic itch can be extremely devastating and, in many cases, difficult to treat. One challenge in treating itch disorders is the limited understanding of the multitude of chemical players involved in the communication of itch sensation from the peripheral to the central nervous system. Neuropeptides are intercellular signaling molecules that are known to be involved in the transmission of itch signals from primary afferent neurons, which detect itch in the skin, to higher-order circuits in the spinal cord and brain. To investigate the role of neuropeptides in transmitting itch signals, we generated two mouse models of chronic itch—Acetone–Ether–Water (AEW, dry skin) and calcipotriol (MC903, atopic dermatitis). For peptide identification and quantitation, we analyzed the peptide content of dorsal root ganglia (DRG) and dorsal horn (DH) tissues from chronically itchy mice using liquid chromatography coupled to tandem mass spectrometry. De novo-assisted database searching facilitated the identification and quantitation of 335 peptides for DH MC903, 318 for DH AEW, 266 for DRG MC903, and 271 for DRG AEW. Of these quantifiable peptides, we detected 30 that were differentially regulated in the tested models, after accounting for multiple testing correction (q≤ 0.1). These include several peptide candidates derived from neuropeptide precursors, such as proSAAS, protachykinin-1, proenkephalin, and calcitonin gene-related peptide, some of them previously linked to itch. The peptides identified in this study may help elucidate our understanding about these debilitating disorders. Data are available via ProteomeXchange with identifier PXD015949.