Brain Region-dependent Heterogeneity and Dose-dependent Difference in Transient Microglia Population Increase during Lipopolysaccharide-induced Inflammation.

Brain Region-dependent Heterogeneity and Dose-dependent Difference in Transient Microglia Population Increase during Lipopolysaccharide-induced Inflammation.
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DOI:
10.1038/s41598-018-20643-3
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发表时间:
2018-02-02
期刊:
影响因子:
4.6
通讯作者:
Miyata S
Miyata S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Furube E;Kawai S;Inagaki H;Takagi S;Miyata S

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许多研究已经报道了小胶质细胞活化在各种病理条件下的重要性,而很少关注感染诱导的炎症下小胶质细胞群体的动力学。在本研究中,100 μg/kg脂多糖(LPS)的单次全身刺激仅在脑室周围器官(CVO)及其邻近脑区诱导了强烈的小胶质细胞增殖。在1 mg/kg LPS刺激后,超过一半的小胶质细胞在CVO及其邻近脑区中同样显示出增殖活性,而这种刺激扩大了小胶质细胞增殖的脑区,包括下丘脑、延髓和边缘系统。小胶质细胞增殖导致小胶质细胞密度的短暂增加,因为它们的密度在3周内几乎恢复到基础水平。分裂的小胶质细胞与未分裂的小胶质细胞存活率相同。增殖的小胶质细胞经常表达驻留的小胶质细胞标记物Tmem 119,表明小胶质细胞密度的增加是由于驻留的小胶质细胞的增殖。因此,本研究表明,在感染诱导的炎症过程中,小胶质细胞密度的瞬时增加取决于脑区域和LPS的剂量,并可能提供一个新的见解小胶质细胞在炎症和脑疾病的发病机制中的功能。
Numerous studies have reported the importance of microglial activation in various pathological conditions, whereas little attention has been given to the point for dynamics of microglial population under infection-induced inflammation. In the present study, the single systemic stimulation of 100 μg/kg lipopolysaccharide (LPS) induced robust microglial proliferation only in the circumventricular organs (CVOs) and their neighboring brain regions. More than half of microglia similarly showed proliferative activity in the CVOs and their neighboring brain regions after 1 mg/kg LPS stimulation, while this stimulation expanded microglia-proliferating brain regions including the hypothalamus, medulla oblongata, and limbic system. Microglia proliferation resulted in a transient increase of microglial density, since their density almost returned to basal levels within 3 weeks. Divided microglia survived at the same rate as non-divided ones. Proliferating microglia frequently expressed a resident microglia marker Tmem119, indicating that increase of microglia density is due to the proliferation of resident microglia. Thus, the present study demonstrates that transient increase in microglia density depends on the brain region and dose of LPS during infection-induced inflammation and could provide a new insight on microglia functions in inflammation and pathogenesis of brain diseases.
耦合的增殖和凋亡维持成人大脑中小胶质细胞的快速离职。
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