Exploring the transcriptome of resident spinal microglia after collagen antibody-induced arthritis.
Exploring the transcriptome of resident spinal microglia after collagen antibody-induced arthritis.
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DOI：
10.1097/j.pain.0000000000001394
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发表时间：
2019-01
期刊：
影响因子：
7.4
通讯作者：
Svensson CI
中科院分区：
文献类型：
--
作者：
Fernandez-Zafra T;Gao T;Jurczak A;Sandor K;Hore Z;Agalave NM;Su J;Estelius J;Lampa J;Hokfelt T;Wiesenfeld-Hallin Z;Xu X;Denk F;Svensson CI
文本中提供了补充数字内容。神经胶质细胞抑制剂只能逆转患有关节炎的雄性小鼠的机械超敏反应。男性和女性脊髓小胶质细胞之间没有发现明显的关节炎相关转录差异。最近的研究表明，脊髓胶质细胞在维持慢性疼痛啮齿动物模型的机械超敏反应中具有性别二态性作用。我们使用胶原抗体诱导关节炎（CAIA）小鼠模型来检查雄性和雌性在关节炎引起的疼痛的脊柱调节方面的差异。我们重点关注该模型的后期阶段，此时关节炎症已经解决，但机械超敏反应仍然存在。尽管脊髓中 P 物质、降钙素基因相关肽和甘丙肽免疫反应性的强度与对照组没有差异，但男性和女性的小胶质细胞 (Iba-1) 和星形胶质细胞（胶质纤维酸性蛋白）标记物的强度均升高。鞘内注射神经胶质抑制剂米诺环素和己酮可可碱可逆转雄性小鼠的机械阈值，但不会逆转雌性小鼠的机械阈值。我们从腰椎背角分离出驻留的小胶质细胞，并通过流式细胞术分析观察到雌性中小胶质细胞的数量显着减少。然而，尽管全基因组 RNA 测序结果表明男性和女性小胶质细胞之间存在一些转录差异，但对照组和 CAIA 组之间没有发现令人信服的差异。综上所述，这些发现表明，小胶质细胞表达谱存在细微的性别差异，与关节炎无关。我们的实验未能确定 CAIA 模型后期小胶质细胞行为的潜在 mRNA 相关性。转录变化可能是微妙且高度局部化的，因此难以通过批量分离技术来识别，或者其他因素（例如蛋白质表达或表观遗传修饰的变化）在起作用。
Supplemental Digital Content is Available in the Text. Glial inhibitors only reverse mechanical hypersensitivity in male mice subjected to arthritis. No obvious arthritis-related transcriptional difference was identified between male and female spinal microglia. Recent studies have suggested a sexually dimorphic role of spinal glial cells in the maintenance of mechanical hypersensitivity in rodent models of chronic pain. We have used the collagen antibody–induced arthritis (CAIA) mouse model to examine differences between males and females in the context of spinal regulation of arthritis-induced pain. We have focused on the late phase of this model when joint inflammation has resolved, but mechanical hypersensitivity persists. Although the intensity of substance P, calcitonin gene–related peptide, and galanin immunoreactivity in the spinal cord was not different from controls, the intensity of microglia (Iba-1) and astrocyte (glial fibrillary acidic protein) markers was elevated in both males and females. Intrathecal administration of the glial inhibitors minocycline and pentoxifylline reversed mechanical thresholds in male, but not in female mice. We isolated resident microglia from the lumbar dorsal horns and observed a significantly lower number of microglial cells in females by flow cytometry analysis. However, although genome-wide RNA sequencing results pointed to several transcriptional differences between male and female microglia, no convincing differences were identified between control and CAIA groups. Taken together, these findings suggest that there are subtle sex differences in microglial expression profiles independent of arthritis. Our experiments failed to identify the underlying mRNA correlates of microglial actions in the late phase of the CAIA model. It is likely that transcriptional changes are either subtle and highly localised and therefore difficult to identify with bulk isolation techniques or that other factors, such as changes in protein expression or epigenetic modifications, are at play.
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影响因子：
4.7
作者：
Altawil, Reem;Saevarsdottir, Saedis;Wedren, Sara;Alfredsson, Lars;Klareskog, Lars;Lampa, Jon
通讯作者：
Lampa, Jon
影响因子：
3.3
作者：
Kosek, Eva;Altawil, Reem;Kadetoff, Diana;Finn, Anja;Westman, Marie;Le Maitre, Ervvan;Andersson, Magnus;Jensen-Urstad, Mats;Lampa, Jon
通讯作者：
Lampa, Jon
影响因子：
11.4
作者：
Cohen, Merav;Matcovitch, Orit;Schwartz, Michal
通讯作者：
Schwartz, Michal
DOI：
10.1073/pnas.0610811104
发表时间：
2007-06-19
影响因子：
11.1
作者：
Clark, Anna K.;Yip, Ping K.;Malcangio, Marzia
通讯作者：
Malcangio, Marzia
影响因子：
3.4
作者：
Dunston, Christopher R.;Griffiths, Helen R.;Lambert, Peter A.;Staddon, Susan;Vernallis, Ann B.
通讯作者：
Vernallis, Ann B.