Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Florence, Italy.
Department of Psychology, The Ohio State University, Columbus, Ohio, USA.
FASEB J. 2019 Mar;33(3):4007-4020. doi: 10.1096/fj.201801539R. Epub 2018 Nov 29.
Aging and neurodegenerative diseases share a condition of neuroinflammation entailing the production of endogenous cell debris in the CNS that must be removed by microglia ( i.e., resident macrophages), to restore tissue homeostasis. In this context, extension of microglial cell branches toward cell debris underlies the mechanisms of microglial migration and phagocytosis. Amoeboid morphology and the consequent loss of microglial branch functionality characterizes dysregulated microglia. Microglial migration is assisted by another glial population, the astroglia, which forms a dense meshwork of cytoplasmic projections. Amoeboid microglia and disrupted astrocyte meshwork are consistent traits in aged CNS. In this study, we assessed a possible correlation between microglia and astroglia morphology in rat models of chronic neuroinflammation and aging, by 3-dimensional confocal analysis implemented with particle analysis. Our findings suggest that a microglia-astroglia interaction occurs in rat hippocampus via cell-cell contacts, mediating microglial cell branching in the presence of inflammation. In aged rats, the impairment of such an interaction correlates with altered distribution, morphology, and inefficient clearance by microglia. These data support the idea that generally accepted functional boundaries between microglia and astrocytes should be re-evaluated to better understand how their functions overlap and interact.-Lana, D., Ugolini, F., Wenk, G. L., Giovannini, M. G., Zecchi-Orlandini, S., Nosi, D. Microglial distribution, branching, and clearance activity in aged rat hippocampus are affected by astrocyte meshwork integrity: evidence of a novel cell-cell interglial interaction.
衰老和神经退行性疾病具有共同的神经炎症状态，涉及中枢神经系统内源性细胞碎片的产生，这些碎片必须被小胶质细胞（即驻留巨噬细胞）清除，以恢复组织内稳态。在这种情况下，小胶质细胞分支向细胞碎片的延伸是小胶质细胞迁移和吞噬的机制基础。阿米巴样形态和小胶质细胞分支功能的丧失是失调小胶质细胞的特征。小胶质细胞的迁移得到另一种神经胶质细胞-星形胶质细胞的协助，星形胶质细胞形成细胞质突起的密集网格。阿米巴样小胶质细胞和星形胶质细胞网格的破坏是衰老中枢神经系统的一致特征。在这项研究中，我们通过三维共聚焦分析和粒子分析评估了慢性神经炎症和衰老大鼠模型中小胶质细胞和星形胶质细胞形态之间的可能相关性。我们的研究结果表明，在炎症存在的情况下，小胶质细胞和星形胶质细胞之间通过细胞-细胞接触发生相互作用，介导小胶质细胞分支。在老年大鼠中，这种相互作用的损伤与小胶质细胞分布、形态和清除效率的改变相关。这些数据支持这样一种观点，即需要重新评估小胶质细胞和星形胶质细胞之间公认的功能边界，以更好地理解它们的功能如何重叠和相互作用。-Lana, D., Ugolini, F., Wenk, G. L., Giovannini, M. G., Zecchi-Orlandini, S., Nosi, D. 老年大鼠海马中小胶质细胞的分布、分支和清除活性受星形胶质细胞网格完整性的影响：一种新型细胞间胶质相互作用的证据。
