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Abstract
Infection with the protozoan Toxoplasma gondii induces changes in neurotransmission, neuroinflammation, and behavior, yet it remains elusive how these changes come about. In this study we investigated how norepinephrine levels are altered by infection. TINEV (Toxoplasma-induced neuronal extracellular vesicles) isolated from infected noradrenergic cells down-regulated dopamine ß-hydroxylase (DBH) gene expression in human and rodent cells. Here we report that intracerebral injection of TINEVs into the brain is sufficient to induce DBH down-regulation and distrupt catecholaminergic signalling. Further, TINEV treatment induced hypermethylation upstream of the DBH gene. An antisense lncRNA to DBH was found in purified TINEV preparations. Paracrine signalling to induce transcriptional gene silencing and DNA methylation may be a common mode to regulate neurologic function.
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Details
1 University of Leeds, School of Biology, Faculty of Biological Sciences, Leeds, UK (GRID:grid.9909.9) (ISNI:0000 0004 1936 8403); University of Cambridge, Department of Clinical Neurosciences, Cambridge, UK (GRID:grid.5335.0) (ISNI:0000000121885934)
2 University of Leeds, School of Biology, Faculty of Biological Sciences, Leeds, UK (GRID:grid.9909.9) (ISNI:0000 0004 1936 8403)
3 Kyoto University, Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto, Japan (GRID:grid.258799.8) (ISNI:0000 0004 0372 2033)
4 University of Leeds, School of Biomedical Sciences, Faculty of Biological Sciences, Leeds, UK (GRID:grid.9909.9) (ISNI:0000 0004 1936 8403)