Developmental stage of oligodendrocytes determines their response to activated microglia in vitro.

Developmental stage of oligodendrocytes determines their response to activated microglia in vitro.
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DOI:
10.1186/1742-2094-4-28
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发表时间:
2007-11-26
影响因子:
9.3
通讯作者:
Beattie MS
Beattie MS
中科院分区:
医学1区
文献类型:
--
作者:
Miller BA;Crum JM;Tovar CA;Ferguson AR;Bresnahan JC;Beattie MS

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少突胶质细胞祖细胞(OPCs)和成熟的少突胶质细胞在中枢神经系统损伤和疾病中均丢失。活化的小胶质细胞可能在OPC和少突胶质细胞的丢失或替代中起作用,但目前尚不清楚OPC和少突胶质细胞对活化的小胶质细胞的反应如何不同。从大鼠皮层分离OPCs和小胶质细胞。用甲状腺激素诱导OPCs向少突胶质细胞分化。对于选定的实验,将小胶质细胞加入OPC或少突胶质细胞培养物中。用脂多糖激活小胶质细胞,并用TNFα ELISA证实小胶质细胞活化。用免疫细胞化学和细胞计数评估细胞存活。还评估了OPC增殖和少突胶质细胞凋亡。OPCs和少突胶质细胞分别表现出代表未成熟和成熟少突胶质细胞的表型。活化的小胶质细胞减少OPC存活,但增加存活和减少成熟少突胶质细胞的凋亡。激活的小胶质细胞也经历了细胞死亡。活化的小胶质细胞可能对OPC和成熟的少突胶质细胞有不同的影响,减少OPC存活和增加成熟的少突胶质细胞存活。这可能是重要的,因为活化的小胶质细胞存在于几种疾病状态中,其中OPCs和成熟的少突胶质细胞也对损伤作出反应。在中枢神经系统损伤后,活化的小胶质细胞可能同时对不同的细胞产生有害和有益的作用。
Oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes are both lost in central nervous system injury and disease. Activated microglia may play a role in OPC and oligodendrocyte loss or replacement, but it is not clear how the responses of OPCs and oligodendrocytes to activated microglia differ. OPCs and microglia were isolated from rat cortex. OPCs were induced to differentiate into oligodendrocytes with thyroid hormone in defined medium. For selected experiments, microglia were added to OPC or oligodendrocyte cultures. Lipopolysaccharide was used to activate microglia and microglial activation was confirmed by TNFα ELISA. Cell survival was assessed with immunocytochemistry and cell counts. OPC proliferation and oligodendrocyte apoptosis were also assessed. OPCs and oligodendrocytes displayed phenotypes representative of immature and mature oligodendrocytes, respectively. Activated microglia reduced OPC survival, but increased survival and reduced apoptosis of mature oligodendrocytes. Activated microglia also underwent cell death themselves. Activated microglia may have divergent effects on OPCs and mature oligodendrocytes, reducing OPC survival and increasing mature oligodendrocyte survival. This may be of importance because activated microglia are present in several disease states where both OPCs and mature oligodendrocytes are also reacting to injury. Activated microglia may simultaneously have deleterious and helpful effects on different cells after central nervous system injury.
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