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Updated: May 6, 2026
An In Vitro Model for Studying Tau Aggregation Using Lentiviral-mediated Transduction of Human Neurons
Published on: May 23, 2019
Expression of Tau40 induces activation of cultured rat microglial cells
Lu Wang1, Qian Jiang, Jiang Chu
1Department 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.
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.
Insights
Microglia activation during aging involves enhanced tau protein. Expressing tau in microglia boosts their migration and cytokine release, suggesting a new role for tau in brain aging and neuroinflammation.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microtubule-associated protein tau accumulates in aging brains and tauopathies.
- Tau presence in microglia is noted, but its functional role remains unclear.
Purpose of the Study:
- To investigate the role of tau protein in microglial activation during aging.
- To determine how tau expression affects microglial function, including migration, phagocytosis, and cytokine secretion.
Main Methods:
- Immunofluorescence staining and fractal dimension analysis in aging rat and mouse brains.
- Transient transfection of tau40 (human 2N/4R tau) into cultured rat microglia.
- Assays for Iba1 levels, phosphorylated tau localization, cytokine secretion, and microglial proliferation, migration, and phagocytosis.
Main Results:
- Aging microglia showed enhanced total and phosphorylated tau immunoreactivity.
- Tau40 expression activated microglia, increased phosphorylated tau at Ser396, and involved PP2A, ERK, and GSK-3β.
- Tau40 promoted microglial migration and phagocytosis, increased IL-1β, IL-6, IL-10, TNF-α, and nitric oxide secretion, but not proliferation.
Conclusions:
- Human 2N/4R tau plays a novel role in activating microglia.
- Tau-induced microglial activation may contribute to neuroinflammation in aging and tauopathies.
