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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Calcium-Binding Proteins / genetics*
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Calcium-Binding Proteins / metabolism
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Cell Movement
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Cells, Cultured
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Extracellular Signal-Regulated MAP Kinases / genetics
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Gene Expression Regulation*
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Glycogen Synthase Kinase 3 / genetics
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Glycogen Synthase Kinase 3 / metabolism
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Glycogen Synthase Kinase 3 beta
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Humans
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Interleukin-10 / genetics
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Interleukin-10 / metabolism
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Interleukin-1beta / genetics
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Interleukin-1beta / metabolism
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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Male
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Membrane Proteins / genetics*
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Membrane Proteins / metabolism
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Microfilament Proteins / genetics*
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Microfilament Proteins / metabolism
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Microglia / cytology
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Microglia / metabolism*
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Nitric Oxide / biosynthesis
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Phagocytosis
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Protein Phosphatase 2 / genetics
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Protein Phosphatase 2 / metabolism
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Rats
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Rats, Sprague-Dawley
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Signal Transduction
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
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p38 Mitogen-Activated Protein Kinases / genetics
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p38 Mitogen-Activated Protein Kinases / metabolism
Substances
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Aif1 protein, rat
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Calcium-Binding Proteins
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Interleukin-1beta
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Interleukin-6
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Membrane Proteins
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Microfilament Proteins
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Tumor Necrosis Factor-alpha
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tau 40 protein, human
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Interleukin-10
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Nitric Oxide
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GSK3B protein, human
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Glycogen Synthase Kinase 3 beta
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Gsk3b protein, mouse
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Gsk3b protein, rat
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Extracellular Signal-Regulated MAP Kinases
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p38 Mitogen-Activated Protein Kinases
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Glycogen Synthase Kinase 3
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Protein Phosphatase 2
Grants and funding
This work was supported in part by grants from the Natural Science Foundation of China (grant number:30971204, 81271404)(
http://www.nsfc.gov.cn/Portal0/default152.htm). No additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.