Transcriptional profile of spinal dynorphin-lineage interneurons in the developing mouse.
Transcriptional profile of spinal dynorphin-lineage interneurons in the developing mouse.
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DOI：
10.1097/j.pain.0000000000001636
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发表时间：
2019-06
期刊：
影响因子：
7.4
通讯作者：
Elizabeth K. Serafin;Alexander G Chamessian;Jie Li;Xiang Zhang;Amanda M. McGann;C. Brewer;T. Berta;M. Baccei
中科院分区：
文献类型：
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作者：
Elizabeth K. Serafin;Alexander G Chamessian;Jie Li;Xiang Zhang;Amanda M. McGann;C. Brewer;T. Berta;M. Baccei
越来越多的证据表明，脊髓背角（SDH）包含多个亚群的抑制性中间神经元，发挥不同的作用，在躯体感觉处理，脊髓强啡肽表达神经元的重要性，抑制机械性疼痛和化学性瘙痒的例证。虽然很明显，在SDH的GABA能传输经历了显着的变化，在出生后的早期发展，鲜为人知的是成熟的离散抑制性“微电路”内的区域。因此，本研究的目标是阐明脊髓强啡肽（pDyn）谱系神经元的基因表达谱在整个生命。我们在出生后第7、21和80天使用特异性细胞类型标记的核分离（INTACT）技术从pDyn-lineage SDH中间神经元特异性地分离核RNA，然后进行RNA-seq分析。与非pDyn脊髓细胞核相比，超过650个基因在成人pDyn细胞核中富集≥2倍，包括已知与疼痛相关的靶点，如甘丙肽（Gal）、前脑啡肽（Pnoc）和一氧化氮合酶1（Nos 1）。此外，编码膜结合鸟苷酸环化酶的基因Gucy 2d被鉴定为SDH内pDyn群体的新型和高选择性标记。差异基因表达分析比较pDyn细胞核在三个年龄组揭示了基因组显着上调（如Cartpt，编码可卡因和安非他明调节转录肽）或下调（包括Npbwr 1，编码神经肽B/W的受体）在出生后的发展。总的来说，这些结果提供了新的见解潜在的分子机制，已知的年龄依赖性变化的脊髓伤害性处理和疼痛敏感性。
Mounting evidence suggests that the spinal dorsal horn (SDH) contains multiple subpopulations of inhibitory interneurons that play distinct roles in somatosensory processing, as exemplified by the importance of spinal dynorphin-expressing neurons for the suppression of mechanical pain and chemical itch. While it is clear that GABAergic transmission in the SDH undergoes significant alterations during early postnatal development, little is known about the maturation of discrete inhibitory "microcircuits" within the region. As a result, the goal of the present study was to elucidate the gene expression profile of spinal dynorphin (pDyn)-lineage neurons throughout life. We isolated nuclear RNA specifically from pDyn-lineage SDH interneurons at postnatal days 7, 21, and 80 using the Isolation of Nuclei Tagged in Specific Cell Types (INTACT) technique, followed by RNA-seq analysis. Over 650 genes were ≥2-fold enriched in adult pDyn nuclei compared to non-pDyn spinal cord nuclei, including targets with known relevance to pain such as galanin (Gal), prepronociceptin (Pnoc), and nitric oxide synthase 1 (Nos1). In addition, the gene encoding a membrane-bound guanylate cyclase, Gucy2d, was identified as a novel and highly selective marker of the pDyn population within the SDH. Differential gene expression analysis comparing pDyn nuclei across the three ages revealed sets of genes that were significantly upregulated (such as Cartpt, encoding cocaine- and amphetamine-regulated transcript peptide) or downregulated (including Npbwr1, encoding the receptor for neuropeptides B/W) during postnatal development. Collectively, these results provide new insight into the potential molecular mechanisms underlying the known age-dependent changes in spinal nociceptive processing and pain sensitivity.