Project description:Background: Although TNF inhibitors are used to treat chronic inflammatory diseases, there is little information about how long-term inhibition of TNF affects the homeostatic functions that TNF maintains in the intact CNS. TNF is known to modulate neurogenesis by decreasing cell proliferation, increasing apoptosis of precursor cells, and impairing neuronal differentiation. TNF can also influence the formation of the hippocampus, with long-lasting effects on cognition. Materials and methods: To clarify whether developmental TNF deficiency causes alterations in the naïve CNS, we estimated the number of proliferating cells, microglia, and neurons in the brains of E13.5, P7, and adult TNF +/+ and TNF-/- mice and measured changes in gene and protein expression and monoamine levels in adult TNF+/+ and TNF-/- mice. To evaluate long-term effects of TNF inhibitors, we treated healthy adult C57BL/6 mice with either saline, selective soluble TNF inhibitor XPro1595, or nonselective TNF inhibitor etanercept. We estimated changes in cell number and protein expression after two months of treatment. We assessed the effects of TNF deficiency on cognition by testing adult TNF+/+ and TNF-/- mice and anti-TNF treated mice with behavioral tasks. Results: TNF deficiency initially decreased the number of proliferating cells and microglia, but subsequently increased the number of neurons. At the same time, TNF deficiency decreased the expression of WNT signaling-related proteins, specifically Collagen Triple Helix Repeat Containing 1 (CTHRC1) and Frizzled receptor 6 (FZD6). In contrast to XPro1595, longterm inhibition of TNF with etanercept in adult C57BL/6 mice decreased the number of proliferating cells in the granule cell layer of the dentate gyrus. Etanercept, but not XPro1595, also impaired spatial learning and memory in the Barnes maze memory test. Conclusion: TNF deficiency impacts the organization of neurogenic zones and alters the cell composition in brain. Long-term inhibition of TNF with the nonselective TNF inhibitor etanercept, but not the soluble TNF inhibitor XPro1595, decreases neurogenesis in the adult mouse hippocampus and impairs learning and memory after two months of treatment.
Project description:Blood (mRNA and miRNA) and skin mRNA transcriptomes were investigated across three time-points in a pilot investigation of ten severe psoriasis patients, treated with the tumor necrosis factor (TNF) inhibitor, etanercept. We used illumina RNA-sequencing to analyse the small-RNA transcriptome in blood
Project description:Blood (mRNA and miRNA) and skin mRNA transcriptomes were investigated across three time-points in a pilot investigation of ten severe psoriasis patients, treated with the tumor necrosis factor (TNF) inhibitor, etanercept. We used illumina RNA-sequencing to analyse the small-RNA transcriptome in blood
Project description:Blood (mRNA and miRNA) and skin mRNA transcriptomes were investigated across three time-points in a pilot investigation of ten severe psoriasis patients, treated with the tumor necrosis factor (TNF) inhibitor, etanercept. We used illumina RNA-sequencing to analyse the mRNA transcriptome in blood
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
