School of Biomedical Sciences and Pharmacy and the Priority Research Centre for Stroke and Brain Injury, University of Newcastle, Callaghan 2308, NSW, Australia; Hunter Medical Research Institute, Newcastle 2305, NSW, Australia.
Hunter Medical Research Institute, Newcastle 2305, NSW, Australia.
Brain Behav Immun. 2018 Feb;68:23-33. doi: 10.1016/j.bbi.2017.09.012. Epub 2017 Sep 22.
Over the last decade, evidence supporting a link between microglia enhanced neuro-inflammatory signalling and mood disturbance has continued to build. One issue that has not been well addressed yet are the factors that drive microglia to enter into a higher pro-inflammatory state. The current study addressed the potential role of the extracellular matrix protein Laminin. C57BL6 adult mice were either exposed to chronic stress or handled for 6 consecutive weeks. Changes in Laminin, microglial morphology and pro-inflammatory cytokine expression were examined in tissue obtained from mice exposed to a chronic restraint stress procedure. These in vivo investigations were complemented by an extensive set of in vitro experiments utilising both a primary microglia and BV2 cell line to examine how Laminin influenced microglial pro-inflammatory tone. Chronic stress enhanced the expression of Laminin, microglial de-ramification and pro-inflammatory cytokine signalling. We further identified that microglia when cultured in the presence of Laminin produced and released significantly greater levels of pro-inflammatory cytokines; took longer to return to baseline following stimulation and exhibited enhanced phagocytic activity. These results suggest that chronic restraint stress is capable of modulating Laminin within the CNS, an effect that has implications for understanding environmental mediated disturbances of microglial function.
在过去的十年中，越来越多的证据表明小胶质细胞增强的神经炎症信号与情绪障碍之间存在关联。然而，仍有一个尚未得到充分解决的问题，即是什么因素导致小胶质细胞进入更高的促炎状态。本研究探讨了细胞外基质蛋白层粘连蛋白的潜在作用。将 C57BL6 成年小鼠暴露于慢性应激或连续处理 6 周。检查了暴露于慢性束缚应激程序的小鼠组织中层粘连蛋白、小胶质细胞形态和促炎细胞因子表达的变化。这些体内研究通过广泛的体外实验得到补充，利用原代小胶质细胞和 BV2 细胞系来研究层粘连蛋白如何影响小胶质细胞的促炎表型。慢性应激增强了层粘连蛋白、小胶质细胞去分支和促炎细胞因子信号的表达。我们进一步发现，当小胶质细胞在层粘连蛋白存在的情况下培养时，会产生和释放出更高水平的促炎细胞因子；在刺激后需要更长的时间才能恢复到基线水平，并表现出增强的吞噬活性。这些结果表明，慢性束缚应激能够调节中枢神经系统中的层粘连蛋白，这对于理解环境介导的小胶质细胞功能障碍具有重要意义。
