Dose-Dependent Microglial Depletion with PLX5622 in Mice

Music City Center 

Dysregulated neuroinflammation is hypothesized to be a leading contributor to neurodegenerative diseases. Microglia, the immune cells of the brain, are crucial in maintaining tissue homeostasis and driving neuroinflammation. Microglia depend on colony-stimulating factor 1 receptor (CSF1R) signaling to survive. CSF1R inhibitors (e.g. PLX5622) are used to deplete microglia in the brain, providing valuable tools for studying microglial dynamics. In this in vivo pharmacology study, we investigate dose-dependent microglial depletion by PLX5622 in wildtype mice (n=48). Six groups of mice (8 mice each: 4 males and 4 females) were treated for 4 weeks with various drug doses (0, 100, 300, 600, 900, or 1200 mg/kg). Whole-brain sections immunostained with Iba1 will be used to quantify microglial depletion and analyzed via one-way ANOVA, with Tukey's post-hoc test to assess dose differences. In surviving microglia, morphological phenotypes, branch length, and soma size will be analyzed using multivariate analysis (MANOVA) and clustering techniques to identify dose-dependent differences. These findings will contribute to understanding microglial dynamics in response to CSF1R inhibition.

Microglial

CSF1R inhibition

Dose-dependent depletion

One-way ANOVA

Tukey’s post-hoc test 

Section on Statistics in Imaging