Identifying the Involvement of Pro-Inflammatory Signal in Hippocampal Gene Expression Changes after Experimental Ischemia: Transcriptome-Wide Analysis
Galina T. Shishkina,
Natalia V. Gulyaeva,
Dmitriy A. Lanshakov,
Tatyana S. Kalinina,
Mikhail V. Onufriev,
Yulia V. Moiseeva,
Ekaterina V. Sukhareva,
Vladimir N. Babenko,
Nikolay N. Dygalo
Affiliations
Galina T. Shishkina
Laboratory of Functional Neurogenomics, Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Science, 630090 Novosibirsk, Russia
Natalia V. Gulyaeva
Laboratory of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485 Moscow, Russia
Dmitriy A. Lanshakov
Laboratory of Functional Neurogenomics, Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Science, 630090 Novosibirsk, Russia
Tatyana S. Kalinina
Laboratory of Functional Neurogenomics, Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Science, 630090 Novosibirsk, Russia
Mikhail V. Onufriev
Laboratory of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485 Moscow, Russia
Yulia V. Moiseeva
Laboratory of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117485 Moscow, Russia
Ekaterina V. Sukhareva
Laboratory of Functional Neurogenomics, Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Science, 630090 Novosibirsk, Russia
Vladimir N. Babenko
Laboratory of Functional Neurogenomics, Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Science, 630090 Novosibirsk, Russia
Nikolay N. Dygalo
Laboratory of Functional Neurogenomics, Federal Research Center Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Science, 630090 Novosibirsk, Russia
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 (Clec5a, CD14, Fgr, Hck, Anxa1, Lgals3, Irf1, Lbp, Ptx3, Serping1) 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.
