Department of Pharmacology, Center of Research in Advance Studies, Mexico City, Mexico.
Brain and Cognition Research Centre (CERCO), CNRS/University of Toulouse, Toulouse, France.
Am J Primatol. 2019 Feb;81(2):e22956. doi: 10.1002/ajp.22956. Epub 2019 Feb 18.
Microglia are cells that protect brain tissue from invading agents and toxic substances, first by releasing pro-inflammatory cytokines, and thereafter by clearing tissue by phagocytosis. Microglia express ferritin, a protein with ferroxidase activity capable of storing iron, a metal that accumulates in brain during aging. Increasing evidence suggests that ferritin plays an important role in inflammation. However, it is not known if ferritin/iron content can be related to the activation state of microglia. To this end, we aimed to delineate the role of ferritin in microglia activation in a non-human primate model. We analyzed brains of male marmosets and observed an increased density of ferritin+ microglia with an activated phenotype in hippocampus and cortex of old marmosets (mean age 11.25 ± 0.70 years) compared to younger subjects. This was accompanied by an increased number of dystrophic microglia in old marmosets. However, in aged subjects (mean age 16.83 ± 2.59 years) the number of ferritin+ microglia was decreased compared to old ones. Meanwhile, the content of iron in brain tissue and cells with oxidized RNA increased during aging in all hippocampal and cortical regions analyzed. Abundant amoeboid microglia were commonly observed surrounding neurons with oxidized RNA. Notably, amoeboid microglia were arginase1+ and IL-10+, indicative of a M2 phenotype. Some of those M2 cells also presented RNA oxidation and a dystrophic phenotype. Therefore, our data suggest that ferritin confers protection to microglia in adult and old marmosets, while in aged subjects the decline in ferritin and the increased amount of iron in brain tissue may be related to the increased number of cells with oxidized RNA, perhaps precluding the onset of neurodegeneration.
小胶质细胞是保护脑组织免受入侵物和有害物质侵害的细胞，首先通过释放促炎细胞因子，然后通过吞噬作用清除组织。小胶质细胞表达铁蛋白，铁蛋白是一种具有亚铁氧化酶活性的蛋白质，能够储存铁，铁在衰老过程中会在大脑中积累。越来越多的证据表明铁蛋白在炎症中发挥重要作用。然而，尚不清楚铁蛋白/铁含量是否与小胶质细胞的激活状态有关。为此，我们旨在阐明铁蛋白在非人灵长类动物模型中小胶质细胞激活中的作用。我们分析了雄性狨猴的大脑，观察到在老年狨猴（平均年龄 11.25±0.70 岁）的海马体和皮质中，铁蛋白+小胶质细胞的密度增加，表现出激活表型，与年轻对象相比。这伴随着老年狨猴中变性小胶质细胞数量的增加。然而，在老年受试者（平均年龄 16.83±2.59 岁）中，铁蛋白+小胶质细胞的数量比老年组减少。与此同时，在所有分析的海马体和皮质区域中，脑组织和氧化 RNA 含量增加的细胞中的铁含量在衰老过程中增加。在氧化 RNA 的神经元周围常见到丰富的阿米巴样小胶质细胞。值得注意的是，阿米巴样小胶质细胞是精氨酸酶 1+和 IL-10+，表明为 M2 表型。这些 M2 细胞中的一些也表现出 RNA 氧化和变性表型。因此，我们的数据表明铁蛋白赋予成年和老年狨猴小胶质细胞保护作用，而在老年受试者中，铁蛋白的下降和脑组织中铁含量的增加可能与氧化 RNA 含量增加的细胞数量有关，这可能阻止了神经退行性变的发生。
