Evaluating the Effect of Interleukin-4 in the 3xTg Mouse Model of Alzheimer's Disease.

ABSTRACT: Chronic neuroinflammation has long been hypothesized to be involved in Alzheimer's Disease (AD) progression. Previous research suggests that both anti-inflammatory and inflammatory microglia ameliorate amyloid pathology, but the latter worsen tau pathology. In this study, we sought to determine whether induction of arginase-1 positive microglia with the anti-inflammatory cytokine IL-4 modulates pathology in the 3xTg mouse model of AD. Our findings indicate that a single intracranial IL-4 injection positively modulated performance of 3xTg AD mice in a Novel Object Recognition task, and locally increased the levels of arginase-1 positive myeloid cells when assessed one-week post injection. Furthermore, immunohistochemical analysis revealed decreased tau phosphorylation in IL-4 injected animals; however, we were not able to detect significant changes in tau phosphorylation utilizing Western blot. Lastly, IL-4 injection did not appear to cause significant changes in amyloid ? load. In conclusion, acute intracranial IL-4 led to some positive benefits in the 3xTg mouse model of AD. Although more work remains, these results support therapeutic strategies aimed at modifying microglial activation states in neurodegenerative diseases.

SUBMITTER: Dionisio-Santos DA 

PROVIDER: S-EPMC7247853 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature