Department of Neurology, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam Neuroscience, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.
Intensive Care Medicine, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
Cells. 2021 Jan 30;10(2):279. doi: 10.3390/cells10020279.
Systemic infection is an important risk factor for the development cognitive impairment and neurodegeneration in older people. Animal experiments show that systemic challenges with live bacteria cause a neuro-inflammatory response, but the effect of age on this response in these models is unknown. Young (2 months) and middle-aged mice (13-14 months) were intraperitoneally challenged with live () or saline. The mice were sacrificed at 2, 3 and 7 days after inoculation; for all time points, the mice were treated with ceftriaxone (an antimicrobial drug) at 12 and 24 h after inoculation. Microglial response was monitored by immunohistochemical staining with an ionized calcium-binding adaptor molecule 1 (Iba-1) antibody and flow cytometry, and inflammatory response by mRNA expression of pro- and anti-inflammatory mediators. We observed an increased microglial cell number and moderate morphologically activated microglial cells in middle-aged mice, as compared to young mice, after intraperitoneal challenge with live . Flow cytometry of microglial cells showed higher CD45 and CD11b expressions in middle-aged infected mice compared to young infected mice. The brain expression levels of pro-inflammatory genes were higher in middle-aged than in young infected mice, while middle-aged infected mice had similar expression levels of these genes in the systemic compartment. We conclude that systemic challenge with live bacteria causes an age-dependent neuro-inflammatory and microglial response. Our data show signs of an age-dependent disconnection of the inflammatory transcriptional signature between the brain and the systemic compartment.
全身性感染是老年人认知障碍和神经退行性变发展的一个重要危险因素。动物实验表明，全身接触活细菌会引起神经炎症反应，但这些模型中年龄对这种反应的影响尚不清楚。年轻（2 个月）和中年（13-14 个月）小鼠经腹腔内接种活 （）或生理盐水。接种后 2、3 和 7 天处死小鼠；所有时间点，在接种后 12 和 24 小时用头孢曲松（一种抗菌药物）处理小鼠。用离子钙结合衔接分子 1（Iba-1）抗体和流式细胞术监测小胶质细胞反应，用促炎和抗炎介质的 mRNA 表达监测炎症反应。我们观察到，与年轻小鼠相比，腹腔内接种活 后，中年小鼠的小胶质细胞数量增加，形态上中度激活的小胶质细胞增多。与年轻感染小鼠相比，中年感染小鼠的小胶质细胞中 CD45 和 CD11b 的表达更高。与年轻感染小鼠相比，中年感染小鼠脑中促炎基因的表达水平更高，而中年感染小鼠在系统隔室中的这些基因表达水平相似。我们得出结论，全身接触活细菌会引起与年龄相关的神经炎症和小胶质细胞反应。我们的数据显示，大脑和系统隔室之间的炎症转录特征存在与年龄相关的脱钩迹象。
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