Ex vivo cultures of microglia from young and aged rodent brain reveal age-related changes in microglial function.
Ex vivo cultures of microglia from young and aged rodent brain reveal age-related changes in microglial function.
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DOI：
10.1016/j.neurobiolaging.2010.05.008
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发表时间：
2012-01
影响因子：
4.2
通讯作者：
Streit WJ
中科院分区：
文献类型：
--
作者：
Njie EG;Boelen E;Stassen FR;Steinbusch HW;Borchelt DR;Streit WJ
为了了解小胶质细胞功能如何随着衰老而变化，已经开发了各种方案来从年轻和老年中枢神经系统（CNS）中分离小胶质细胞。在这里，我们报告修改现有的协议，其特点是减少碎片污染和提高产量，并表明小胶质细胞的功能是多种多样的，并依赖于年龄。具体来说，我们发现，相对于年轻小鼠的小胶质细胞，老年小鼠的小胶质细胞组成性分泌更大量的白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α），并且对刺激的反应较低。此外，来自老年小鼠的小胶质细胞具有降低的谷胱甘肽水平，并且内化较少的淀粉样β肽（Aβ），而来自所有年龄的小鼠的小胶质细胞不保留淀粉样β肽显著的时间长度。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。他们认为，小胶质细胞Aβ吞噬作用导致Aβ重新分布，而不是体内生物物理降解，从而为老年人和阿尔茨海默病患者的实质小胶质细胞缺乏淀粉样蛋白负荷消除提供了机制性见解。
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 demonstrates 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.
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影响因子：
5.3
作者：
Hickman, Suzanne E.;Allison, Elizabeth K.;El Khoury, Joseph
通讯作者：
El Khoury, Joseph
DOI：
10.1097/00004647-199802000-00008
发表时间：
1998-02-01
影响因子：
6.3
作者：
Loddick, SA;Turnbull, AV;Rothwell, NJ
通讯作者：
Rothwell, NJ
影响因子：
2.5
作者：
Culpan, D;MacGowan, SH;Wilcock, GK
通讯作者：
Wilcock, GK
影响因子：
2.9
作者：
Hirrlinger, J;Gutterer, JM;Dringen, R
通讯作者：
Dringen, R
影响因子：
5.3
作者：
Jung, S;Aliberti, J;Littman, DR
通讯作者：
Littman, DR