Shishkina Galina T, Gulyaeva Natalia V, Lanshakov Dmitriy A, Kalinina Tatyana S, Onufriev Mikhail V, Moiseeva Yulia V, Sukhareva Ekaterina V, Babenko Vladimir N, Dygalo Nikolay N
Laboratory of Functional Neurogenomics, Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Science, 630090 Novosibirsk, Russia.
Laboratory of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485 Moscow, Russia.
Biomedicines. 2021 Dec 5;9(12):1840. doi: 10.3390/biomedicines9121840.
Acute cerebral ischemia induces distant inflammation in the hippocampus; however, molecular mechanisms of this phenomenon remain obscure. Here, hippocampal gene expression profiles were compared in two experimental paradigms in rats: middle cerebral artery occlusion (MCAO) and intracerebral administration of lipopolysaccharide (LPS). The main finding is that 10 genes () may represent key molecular links underlying acute activation of immune cells in the hippocampus in response to experimental ischemia. Functional annotation clustering revealed that these genes built the same clusters related to innate immunity/immunity/innate immune response in all MCAO differentially expressed genes and responded to the direct pro-inflammatory stimulus group. The gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses also indicate that LPS-responding genes were the most abundant among the genes related to "positive regulation of tumor necrosis factor biosynthetic process", "cell adhesion", "TNF signaling pathway", and "phagosome" as compared with non-responding ones. In contrast, positive and negative "regulation of cell proliferation" and "HIF-1 signaling pathway" mostly enriched with genes that did not respond to LPS. These results contribute to understanding genomic mechanisms of the impact of immune/inflammatory activation on expression of hippocampal genes after focal brain ischemia.
急性脑缺血会在海马体中引发远处炎症；然而，这一现象的分子机制仍不清楚。在此，我们在大鼠的两种实验范式中比较了海马体基因表达谱：大脑中动脉闭塞（MCAO）和脑内注射脂多糖（LPS）。主要发现是，10个基因（）可能代表了海马体中免疫细胞在实验性缺血反应中急性激活的关键分子联系。功能注释聚类显示，在所有MCAO差异表达基因中，这些基因形成了与先天免疫/免疫/先天免疫反应相关的相同聚类，并对直接促炎刺激组有反应。基因本体富集分析和京都基因与基因组百科全书通路分析还表明，与无反应基因相比，在与“肿瘤坏死因子生物合成过程的正调控”、“细胞黏附”、“TNF信号通路”和“吞噬体”相关的基因中，对LPS有反应的基因最为丰富。相比之下，“细胞增殖的正调控”和“负调控”以及“HIF-1信号通路”大多富集了对LPS无反应的基因。这些结果有助于理解免疫/炎症激活对局灶性脑缺血后海马体基因表达影响的基因组机制。
