Figure 4

Osteoarthritis exacerbates neuroinflammation in the presence of Aβ pathology. (A) Four month old APP/PS1 transgenic mice displayed low numbers of GFAP positive astrocytes. (B) The induction of osteoarthritis in the APP/PS1 mouse model resulted in greater number of GFAP⁺ astrocytes at the 4 month time point. (C) Eight month old APP/PS1 transgenic mice displayed low numbers of GFAP positive astrocytes, whereas (D) animals suffering from osteoarthritis presented with a greater number of reactive astrocytes as evaluated by GFAP immunohistochemistry. Moreover, (E) we observed only a few MHC-II positive cells in the brain of 4 month old APP/PS1 mice, whereas (F) a larger number was noted throughout the brain of Col1-IL1β^XAT;APP/PS1 mice with osteoarthritis at the 4 month time point. (G) At eight months of age, we observed only a small number of MHC-II positive cells in APP/PS1 mice, whereas (H) a larger number was noted throughout the brain of Col1-IL1β^XAT;APP/PS1 mice with osteoarthritis. (I) MHC-II and GFAP positive cells were quantified in the brains of 8 month wild type (WT), APP/PS1 (AD), Col1-IL1β^XAT mice with osteoarthritis (OA), and Col1-IL1β^XAT;APP/PS1 mice with osteoarthritis (AD+OA). (J) Transcript levels for neuroinflammatory genes at 8 months of age were evaluated by real-time qRT-PCR in Col1-IL1β^XAT;APP/PS1 mice injected with FIV(Cre), FIV(gfp), or saline, as well as wild type mice receiving saline (WT+sal). We observed an upregulation of glial cell activation in the Col1-IL1β^XAT;APP/PS1 mice with osteoarthritis. Mean ± SEM shown, ***p < 0.001; Bar = 100 μm.