Ritzel Rodney M, Patel Anita R, Pan Sarah, Crapser Joshua, Hammond Matt, Jellison Evan, McCullough Louise D
Department of Neurology, University of Connecticut Health Center, Farmington, CT, USA.
Department of Immunology, University of Connecticut Health Center, Farmington, CT, USA.
Neurobiol Aging. 2015 Jun;36(6):2153-63. doi: 10.1016/j.neurobiolaging.2015.02.016. Epub 2015 Feb 23.
Inflammation in the central nervous system (CNS) is primarily regulated by microglia. No longer considered a homogenous population, microglia display a high degree of heterogeneity, immunological diversity and regional variability in function. Given their low rate of self-renewal, the microenvironment in which microglia reside may play an important role in microglial senescence. This study examines age-related changes in microglia in the brain and spinal cord. Using ex-vivo flow cytometry analyses, functional assays were performed to assess changes in microglial morphology, oxidative stress, cytokine production, and phagocytic activity with age in both the brain and spinal cord. The regional CNS environment had a significant effect on microglial activity with age. Blood-CNS barrier permeability was greater in the aging spinal cord compared with aging brain; this was associated with increased tissue cytokine levels. Aged microglia had deficits in phagocytosis at baseline and after stimulus-induced activation. The identification of age-specific, high scatter microglia together with the use of ex-vivo functional analyses provides the first functional characterization of senescent microglia. Age and regional-specificity of CNS disease should be taken into consideration when developing immune-modulatory treatments.
中枢神经系统（CNS）中的炎症主要由小胶质细胞调节。小胶质细胞不再被认为是同质群体，而是表现出高度的异质性、免疫多样性和功能的区域变异性。鉴于其自我更新率较低，小胶质细胞所处的微环境可能在小胶质细胞衰老中起重要作用。本研究考察了脑和脊髓中小胶质细胞与年龄相关的变化。通过体外流式细胞术分析，进行功能测定以评估脑和脊髓中小胶质细胞形态、氧化应激、细胞因子产生及吞噬活性随年龄的变化。中枢神经系统区域环境对小胶质细胞随年龄增长的活性有显著影响。与衰老的脑相比，衰老脊髓中的血脑屏障通透性更高；这与组织细胞因子水平升高有关。衰老的小胶质细胞在基线时以及刺激诱导激活后吞噬作用存在缺陷。鉴定年龄特异性、高散射小胶质细胞并结合体外功能分析首次对衰老小胶质细胞进行了功能表征。在开发免疫调节治疗方法时应考虑中枢神经系统疾病的年龄和区域特异性。
