Figure 1. APP/PS1 and WT mice respond differentially to LPS.

(A) Timeline of the experiment measuring the hippocampal metabolic response to LPS; inset: voxel placement. WT and APP/PS1 mice were subjected to two baseline MRS scans in a region of interest covering the hippocampus prior to receiving a tail vein injection of lipopolysaccharide (LPS, 100 μg/kg) or its vehicle (phosphate buffer saline, PBS). The metabolic response to the intervention was monitored for 4 hours. (B) Representative MRS spectrum (top), the fitted spectrum (blue), the residuals (bottom, black) and individual metabolite fitted spectra for myoinositol (mI) and macromolecules and lipids at 0.9 ppm (ML9). (C) Mean ± SEM percent changes in ML9 levels relative to sum of selected metabolites. In WT mice, LPS induced a sustained increase in ML9 levels which was not observed in APP/PS1 mice. (D) Mean ± SEM percent changes in mI levels relative to sum of selected metabolites. In APP/PS1 mice, LPS significantly increased mI levels at 1 and 4 hours post injection. (E) Representative Iba1 positive microglia (40× magnification) shown for WT (top row) and APP/PS1 (bottom row) mice, 4 hours after injection of either PBS (left) or LPS (right). (F) Mean ± SEM soma size. Microglia activation, reflected by an increase in soma size, occurred in response to LPS in WT but not APP/PS1mice. Changes in soma size were (G) negatively correlated to ML9 in APP/PS1 mice at 2 hours (r = −0.575, p = 0.02), but positively correlated to ML9 in WT at (H) 3 h (r = 0.514, p = 0.035) and (I) 4 h (r = 0.64, p = 0.005) suggesting that microglia activation is associated with increasing ML9. *p < 0.05, **p < 0.01 compared with PBS; ^#p < 0.05, ^##p < 0.01 compared with baseline levels.