UM
Deficiency of macrophage migration inhibitory factor attenuates tau hyperphosphorylation in mouse models of Alzheimer's disease
Li S.-Q.3; Yu Y.3; Han J.-Z.3; Wang D.3; Liu J.3; Qian F.3; Fan G.-H.1; Bucala R.2; Ye R.D.3
2015-09-17
Source PublicationJournal of Neuroinflammation
ISSN17422094
Volume12Issue:1
AbstractBackground: 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.
KeywordAlzheimer's disease Astrocyte activation Macrophage migration inhibitory factor Tau phosphorylation
DOI10.1186/s12974-015-0396-3
URLView the original
Language英語
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Cited Times [WOS]:19   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.GlaxoSmithKline, China
2.Yale University School of Medicine
3.Shanghai Jiao Tong University
4.University of Macau
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GB/T 7714
Li S.-Q.,Yu Y.,Han J.-Z.,et al. Deficiency of macrophage migration inhibitory factor attenuates tau hyperphosphorylation in mouse models of Alzheimer's disease[J]. Journal of Neuroinflammation,2015,12(1).
APA Li S.-Q..,Yu Y..,Han J.-Z..,Wang D..,Liu J..,...&Ye R.D..(2015).Deficiency of macrophage migration inhibitory factor attenuates tau hyperphosphorylation in mouse models of Alzheimer's disease.Journal of Neuroinflammation,12(1).
MLA Li S.-Q.,et al."Deficiency of macrophage migration inhibitory factor attenuates tau hyperphosphorylation in mouse models of Alzheimer's disease".Journal of Neuroinflammation 12.1(2015).
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