Jung Hyeji, Lee Hyojeong, Kim Dongwook, Cheong Eunji, Hyun Young-Min, Yu Je-Wook, Um Ji Won
Department of Brain Sciences, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, 42988, Korea.
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Korea.
J Inflamm Res. 2022 May 23;15:3053-3063. doi: 10.2147/JIR.S362006. eCollection 2022.
Peripheral inflammation-triggered mild neuroinflammation impacts the brain and behavior through microglial activation. In this study, we performed an unbiased analysis of the vulnerability of different brain areas to neuroinflammation induced by systemic inflammation.
We injected mice with a single low dose of LPS to induce mild inflammation and then analyzed microglial activation in 34 brain regions by immunohistochemical methods and whole-brain imaging using multi-slide scanning microscopy. We also conducted quantitative RT-PCR to measure the levels of inflammatory cytokines in selected brain regions of interest.
We found that microglia in different brain regions are differentially activated by mild, LPS-induced inflammation relative to the increase in microglia numbers or increased CD68 expression. The increased number of microglia induced by mild inflammation was not attributable to infiltration of peripheral immune cells. In addition, microglia residing in brain regions, in which a single low-dose injection of LPS produced microglial changes, preferentially generated pro-inflammatory cytokines.
Our results suggest that mild neuroinflammation induces regionally different microglia activation, producing pro-inflammatory cytokines. Our observations provide insight into induction of possible region-specific neuroinflammation-associated brain pathologies through microglial activation.
外周炎症引发的轻度神经炎症通过小胶质细胞激活影响大脑和行为。在本研究中，我们对不同脑区对全身炎症诱导的神经炎症的易感性进行了无偏分析。
我们给小鼠注射单次低剂量脂多糖以诱导轻度炎症，然后通过免疫组织化学方法和使用多玻片扫描显微镜的全脑成像分析34个脑区的小胶质细胞激活情况。我们还进行了定量逆转录聚合酶链反应以测量选定感兴趣脑区中炎性细胞因子的水平。
我们发现，相对于小胶质细胞数量的增加或CD68表达的增加，不同脑区的小胶质细胞对轻度脂多糖诱导的炎症有不同程度的激活。轻度炎症诱导的小胶质细胞数量增加并非归因于外周免疫细胞的浸润。此外，在单次低剂量注射脂多糖会产生小胶质细胞变化的脑区中的小胶质细胞优先产生促炎细胞因子。
我们的结果表明，轻度神经炎症会诱导区域不同的小胶质细胞激活，产生促炎细胞因子。我们的观察结果为通过小胶质细胞激活诱导可能的区域特异性神经炎症相关脑病变提供了见解。
