Department of Applied Biology, Kyoto, 606-8585, Japan.
The Center for Advanced Insect Research Promotion, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan.
Sci Rep. 2018 Feb 2;8(1):2203. doi: 10.1038/s41598-018-20643-3.
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.
大量研究报道了小胶质细胞激活在各种病理条件下的重要性，而对于感染诱导的炎症中小胶质细胞群体动态的关注甚少。在本研究中，100μg/kg 脂多糖（LPS）的单次全身刺激仅在室周器官（CVOs）及其邻近脑区诱导强烈的小胶质细胞增殖。在 1mg/kg LPS 刺激后，CVOs 及其邻近脑区中超过一半的小胶质细胞表现出类似的增殖活性，而这种刺激扩大了包括下丘脑、延髓和边缘系统在内的小胶质细胞增殖脑区。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以相同的速度存活。增殖的小胶质细胞经常表达驻留小胶质细胞标志物 Tmem119，表明小胶质细胞密度的增加是由于驻留小胶质细胞的增殖。因此，本研究表明，感染诱导的炎症中小胶质细胞密度的短暂增加取决于 LPS 的脑区和剂量，并为小胶质细胞在炎症和脑部疾病发病机制中的功能提供了新的见解。
