Aging and sex: Impact on microglia phagocytosis
Aging and sex: Impact on microglia phagocytosis
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DOI：
10.1111/acel.13182
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发表时间：
2020-07
期刊：
影响因子：
7.8
通讯作者：
Natalia Yanguas-Casás;Andrea Crespo-Castrillo;M. Arevalo;L. Garcia-Segura
中科院分区：
文献类型：
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作者：
Natalia Yanguas-Casás;Andrea Crespo-Castrillo;M. Arevalo;L. Garcia-Segura
小胶质细胞功能障碍和激活是大脑老化的重要标志，并伴随着年龄相关的神经变性和认知能力下降。小胶质细胞迁移和吞噬能力的年龄相关变化导致适应不良反应、慢性神经炎症和神经退行性疾病结局恶化。考虑到大多数神经系统疾病的发病率、患病率和治疗反应存在性别偏见，我们在这里研究了老年小胶质细胞的吞噬活性在男性和女性中是否不同。为此，在体外老化小胶质细胞模型和从成年（5月龄）或老化（18月龄）小鼠分离的小胶质细胞中比较了雄性和雌性细胞的吞噬活性。在这两种模型中，神经碎片的吞噬作用随着年龄的增长而增加，在男性和女性细胞中，老年女性小胶质细胞的吞噬作用高于老年男性细胞。然而，雌性老年小胶质细胞失去了适应炎症条件的吞噬活性的能力。这些研究结果表明，小胶质细胞吞噬神经碎片可能代表了一个以前未探索的神经保护功能的老年小胶质细胞，可能有助于产生性别差异的神经退行性疾病的表现。
Microglia dysfunction and activation are important hallmarks of the aging brain and are concomitant with age‐related neurodegeneration and cognitive decline. Age‐associated changes in microglia migration and phagocytic capacity result in maladaptive responses, chronic neuroinflammation, and worsened outcomes in neurodegenerative disorders. Given the sex bias in the incidence, prevalence, and therapy response of most neurological disorders, we have here examined whether the phagocytic activity of aged microglia is different in males and females. With this aim, the phagocytosis activity of male and female cells was compared in an in vitro aged microglia model and in microglia isolated from adult (5‐month‐old) or aged (18‐month‐old) mice. In both models, the phagocytosis of neural debris increased with aging in male and female cells and was higher in aged female microglia than in aged male cells. However, female aged microglia lost its ability to adapt its phagocytic activity to inflammatory conditions. These findings suggest that microglia phagocytosis of neural debris may represent a previously unexplored neuroprotective characteristic of aged microglia that may contribute to the generation of sex differences in the manifestation of neurodegenerative diseases.