Related Experiment Video
Updated: Apr 3, 2026
Cell-based Assay to Study Antibody-mediated Tau Clearance by Microglia
Published on: November 9, 2018
Deficiency of macrophage migration inhibitory factor attenuates tau hyperphosphorylation in mouse models of
Shu-Qin Li1, Yang Yu2, Jin-Zhao Han3
1School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, China. shuqinliky@163.com.
Background:
Pathological features of Alzheimer's disease (AD) include aggregation of amyloid beta (Aβ) and tau protein. Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, has been implicated in the toxicity of aggregated Aβ. It remains unclear whether MIF affects hyperphosphorylation and aggregation of tau.
Methods:
The effects of MIF deficiency in tau hyperphosphorylation were examined in Mif (-/-) mice receiving intracerebroventricular (ICV) injection of streptozotocin (STZ) and in APP/PS1 transgenic mice mated with Mif (-/-) mice. MIF expression and astrocyte activation were evaluated in ICV-STZ mice using immunofluorescence staining. Cultured primary astrocytes were treated with high glucose to mimic STZ function in vitro, and the condition medium (CM) was collected. The level of tau hyperphosphorylation in neurons treated with the astrocyte CM was determined using Western blotting.
Results:
MIF deficiency attenuated tau hyperphosphorylation in mice. ICV injection of STZ increased astrocyte activation and MIF expression in the hippocampus. MIF deficiency attenuated astrocyte activation in ICV-STZ mice. CM from high glucose-treated WT astrocytes increased tau hyperphosphorylation in cultured primary neurons, an effect absent from Mif (-/-) astrocytes and WT astrocytes treated with the MIF inhibitor ISO-1. ISO-1 had no direct effect on tau phosphorylation in cultured primary neurons.
Conclusions:
These results suggest that MIF deficiency is associated with reduced astrocyte activation and tau hyperphosphorylation in the mouse AD models tested. Inhibition of MIF and MIF-induced astrocyte activation may be useful in AD prevention and therapy.
Insights
Macrophage migration inhibitory factor (MIF) deficiency reduces tau hyperphosphorylation in mouse Alzheimer's disease models. Inhibiting MIF and associated astrocyte activation may offer therapeutic benefits for Alzheimer's disease prevention.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Alzheimer's disease (AD) pathology involves amyloid beta (Aβ) and tau protein aggregation.
- Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, contributes to Aβ toxicity.
- The role of MIF in tau hyperphosphorylation and aggregation remains largely unknown.
Purpose of the Study:
- To investigate the effect of MIF deficiency on tau hyperphosphorylation in mouse models of Alzheimer's disease.
- To examine the relationship between MIF, astrocyte activation, and tau pathology.
Main Methods:
- Utilized Mif (-/-) mice and APP/PS1 transgenic mice crossed with Mif (-/-) mice.
- Administered intracerebroventricular (ICV) streptozotocin (STZ) to induce AD-like pathology.
- Assessed MIF expression and astrocyte activation via immunofluorescence.
- Investigated tau hyperphosphorylation in cultured neurons treated with astrocyte-conditioned medium (CM) from high glucose-exposed astrocytes, with and without MIF inhibition (ISO-1).
Main Results:
- MIF deficiency significantly attenuated tau hyperphosphorylation in mouse models.
- STZ injection increased hippocampal astrocyte activation and MIF expression.
- MIF deficiency reduced astrocyte activation in STZ-injected mice.
- Conditioned medium from high glucose-treated astrocytes induced tau hyperphosphorylation in neurons; this effect was abolished by MIF deficiency or ISO-1 treatment.
Conclusions:
- MIF deficiency is linked to decreased astrocyte activation and reduced tau hyperphosphorylation in tested mouse AD models.
- Inhibiting MIF and MIF-driven astrocyte activation presents a potential therapeutic strategy for Alzheimer's disease prevention and treatment.
