title: Expression of Tau40 induces activation of cultured rat microglial cells.
abstract: Accumulation of microtubule-associated protein tau has been observed in the brain of aging and tauopathies. Tau was observed in microglia, but its role is not illustrated. By immunofluorescence staining and the fractal dimension value assay in the present study, we observed that microglia were activated in the brains of rats and mice during aging, simultaneously, the immunoreactivities of total tau and the phosphorylated tau were significantly enhanced in the activated microglia. Furtherly by transient transfection of tau40 (human 2N/4R tau) into the cultured rat microglia, we demonstrated that expression of tau40 increased the level of Iba1, indicating activation of microglia. Moreover, expression of tau40 significantly enhanced the membranous localization of the phosphorylated tau at Ser396 in microglia possibly by a mechanism involving protein phosphatase 2A, extracellular signal-regulated kinase and glycogen synthase kinase-3β. It was also found that expression of tau40 promoted microglial migration and phagocytosis, but not proliferation. And we observed increased secretion of several cytokines, including interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor-α and nitric oxide after the expression of tau40. These data suggest a novel role of human 2N/4R tau in microglial activation.
authors.affiliation: Department of Pathophysiology, Key Laboratory of Ministry of Education of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China ; Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.forename: Jiang
authors.initials: J
authors.lastname: Chu
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Li
authors.forename: Gao-Shang
authors.initials: GS
authors.lastname: Chai
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Jian-Zhi
authors.initials: JZ
authors.lastname: Wang
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D010587:Phagocytosis; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins
chemical_list: D002135:Calcium-Binding Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D016753:Interleukin-10; D053583:Interleukin-1beta; D015850:Interleukin-6; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009569:Nitric Oxide; D054648:Protein Phosphatase 2; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; C100745:Aif1 protein, rat; C000605506:GSK3B protein, human; C000605507:Gsk3b protein, mouse; C000605508:Gsk3b protein, rat; C054369:MAPT protein, human; D016875:tau Proteins