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Characterization of macrophages from schizophrenia patients
npj Schizophrenia ( IF 5.4 ) Pub Date : 2017-11-14 , DOI: 10.1038/s41537-017-0042-4
Paul R. Ormel , Hans C. van Mierlo , Manja Litjens , Miriam E. van Strien , Elly M. Hol , René S. Kahn , Lot D. de Witte

Genetic, epidemiological and post mortem studies have described an association between schizophrenia (SCZ) and the immune system. Microglia, the tissue-resident macrophages of the brain, not only play an essential role in inflammatory processes, but also in neurodevelopment and synapse refinement. It has therefore been hypothesized that aberrant functioning of these myeloid immune cells is involved in SCZ pathogenesis. Until now cellular research into the role of myeloid cells in SCZ has been limited to monocytes and functional assays are lacking. In this study we used monocyte-derived macrophages (mo-MΦs) as a model for macrophages and microglia in the CNS and examined two main functions: Inflammatory responses and expression and regulation of synapse refinement molecules. The expression of 24 genes involved in these key functions was assessed. Mo-MΦs were generated from 15 SCZ patients and 15 healthy controls. The cells were exposed to pro-inflammatory and anti-inflammatory stimuli (LPS, R848, IL-4 and dexamethasone), and the response was measured by qPCR and ELISA analyses. One of the genes of interest, P2RX7 that is associated with psychiatric diseases, was significantly reduced in expression after LPS stimulation in SCZ patients. None of the other assessed characteristics were different in this functional screen between mo-MΦs from SCZ patients compared to controls. Although these data suggest that overall the function of macrophages in SCZ is not impaired, further studies with larger groups that enable the possibility to study clinical subgroups and perform additional screenings to asses the full phenotype of the mo-MΦs are needed to strengthen this conclusion.



中文翻译:

精神分裂症患者巨噬细胞的表征

遗传,流行病学和验尸研究描述了精神分裂症(SCZ)与免疫系统之间的关联。小胶质细胞是大脑的组织内巨噬细胞,不仅在炎症过程中起着至关重要的作用,而且在神经发育和突触细化中也起着至关重要的作用。因此,已经假设这些髓样免疫细胞的异常功能参与了SCZ的发病机理。迄今为止,细胞对SCZ中髓样细胞作用的研究仅限于单核细胞,缺乏功能测定。在这项研究中,我们使用单核细胞衍生的巨噬细胞(mo-MΦs)作为中枢神经系统巨噬细胞和小胶质细胞的模型,并研究了两个主要功能:炎症反应以及突触细化分子的表达和调控。评估了涉及这些关键功能的24个基因的表达。Mo-MΦ是从15位SCZ患者和15位健康对照中产生的。将细胞暴露于促炎和抗炎刺激(LPS,R848,IL-4和地塞米松),并通过qPCR和ELISA分析测量反应。感兴趣的基因之一LZ刺激SCZ患者后,与精神疾病相关的P2RX7的表达显着降低。与对照组相比,SCZ患者的mo-MΦ在此功能筛查中的其他评估特征均无差异。尽管这些数据表明巨噬细胞在SCZ中的总体功能并未受到损害,但仍需要对更大的群体进行进一步研究,以便能够研究临床亚组并进行额外的筛查以评估mo-MΦ的完整表型,以加强这一结论。

更新日期:2019-11-18
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