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Quantitative Characterization of the Neuropeptide Level Changes in Dorsal Horn and Dorsal Root Ganglia Regions of the Murine Itch Models.
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2020-01-19 , DOI: 10.1021/acs.jproteome.9b00758 Emily G Tillmaand , Krishna D B Anapindi , Eduardo A De La Toba , Changxiong J Guo 1 , Jessica Krebs , Ashley E Lenhart , Qin Liu 1 , Jonathan V Sweedler
Journal of Proteome Research ( IF 3.8 ) Pub Date : 2020-01-19 , DOI: 10.1021/acs.jproteome.9b00758 Emily G Tillmaand , Krishna D B Anapindi , Eduardo A De La Toba , Changxiong J Guo 1 , Jessica Krebs , Ashley E Lenhart , Qin Liu 1 , Jonathan V Sweedler
Affiliation
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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.
中文翻译：
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。
慢性瘙痒可能极具破坏性，并且在许多情况下难以治疗。治疗瘙痒症的一大挑战是对参与从外周神经系统到中枢神经系统的瘙痒感传递的多种化学物质的了解有限。神经肽是细胞间信号分子，已知参与从初级传入神经元（检测皮肤瘙痒）到脊髓和大脑中的高级回路的瘙痒信号的传递。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：丙酮乙醚水（AEW，干性皮肤）和卡泊三醇（MC903，特应性皮炎）。为了进行肽鉴定和定量，我们使用液相色谱结合串联质谱分析了慢性瘙痒小鼠的背根神经节（DRG）和背角（DH）组织的肽含量。从头辅助数据库搜索促进了 DH MC903 的 335 个肽、DH AEW 的 318 个肽、DRG MC903 的 266 个肽和 DRG AEW 的 271 个肽的鉴定和定量。在考虑多重测试校正 (q ≤ 0.1) 后，在这些可量化的肽中，我们检测到 30 种在测试模型中受到差异调节。其中包括几种源自神经肽前体的候选肽，例如 proSAAS、protachykinin-1、脑啡肽原和降钙素基因相关肽，其中一些先前与瘙痒有关。本研究中鉴定的肽可能有助于阐明我们对这些使人衰弱的疾病的理解。数据可通过 ProteomeXchange 获得，标识符为 PXD015949。
更新日期：2020-02-04
中文翻译：
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。
慢性瘙痒可能极具破坏性，并且在许多情况下难以治疗。治疗瘙痒症的一大挑战是对参与从外周神经系统到中枢神经系统的瘙痒感传递的多种化学物质的了解有限。神经肽是细胞间信号分子，已知参与从初级传入神经元（检测皮肤瘙痒）到脊髓和大脑中的高级回路的瘙痒信号的传递。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：丙酮乙醚水（AEW，干性皮肤）和卡泊三醇（MC903，特应性皮炎）。为了进行肽鉴定和定量，我们使用液相色谱结合串联质谱分析了慢性瘙痒小鼠的背根神经节（DRG）和背角（DH）组织的肽含量。从头辅助数据库搜索促进了 DH MC903 的 335 个肽、DH AEW 的 318 个肽、DRG MC903 的 266 个肽和 DRG AEW 的 271 个肽的鉴定和定量。在考虑多重测试校正 (q ≤ 0.1) 后，在这些可量化的肽中，我们检测到 30 种在测试模型中受到差异调节。其中包括几种源自神经肽前体的候选肽，例如 proSAAS、protachykinin-1、脑啡肽原和降钙素基因相关肽，其中一些先前与瘙痒有关。本研究中鉴定的肽可能有助于阐明我们对这些使人衰弱的疾病的理解。数据可通过 ProteomeXchange 获得，标识符为 PXD015949。
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