Department of Neuroscience, University of Florida College of Medicine and McKnight Brain Institute, Gainesville, FL 32610-0244, United States.
Neurobiol Aging. 2012 Jan;33(1):195.e1-12. doi: 10.1016/j.neurobiolaging.2010.05.008. Epub 2010 Jul 2.
To understand how microglial cell function may change with aging, various protocols have been developed to isolate microglia from the young and aged central nervous system (CNS). Here we report modification of an existing protocol that is marked by less debris contamination and improved yields and demonstrate that microglial functions are varied and dependent on age. Specifically, we found that microglia from aged mice constitutively secrete greater amounts of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) relative to microglia from younger mice and are less responsive to stimulation. Also, microglia from aged mice have reduced glutathione levels and internalize less amyloid beta peptide (Aβ) while microglia from mice of all ages do not retain the amyloid beta peptide for a significant length of time. These studies offer further support for the idea that microglial cell function changes with aging. They suggest that microglial Aβ phagocytosis results in Aβ redistribution rather than biophysical degradation in vivo and thereby provide mechanistic insight to the lack of amyloid burden elimination by parenchymal microglia in aged adults and those suffering from Alzheimer's disease.
为了了解小胶质细胞功能随衰老而发生的变化，人们开发了各种方案，从小鼠的年轻和老年中枢神经系统（CNS）中分离小胶质细胞。在此，我们报告了一种现有方案的改进，该方案的特点是碎屑污染更少、产量提高，并证明小胶质细胞的功能是多样的，且依赖于年龄。具体而言，我们发现，与年轻小鼠的小胶质细胞相比，老年小鼠的小胶质细胞持续分泌更多的白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α），且对刺激的反应性降低。此外，老年小鼠的小胶质细胞谷胱甘肽水平降低，内化的淀粉样β肽（Aβ）较少，而所有年龄段的小鼠的小胶质细胞都不会在很长一段时间内保留 Aβ。这些研究进一步支持了小胶质细胞功能随衰老而变化的观点。它们表明，小胶质细胞 Aβ吞噬作用导致 Aβ重新分布，而不是体内的生物物理降解，从而为实质性小胶质细胞在老年和阿尔茨海默病患者中未能消除淀粉样蛋白负担提供了机制上的见解。
