Fig. 4

Depletion of microglia attenuates the protective effects of sTREM2 on Aβ pathology and synaptic plasticity. a Scheme for PLX3397 administration and sTREM2 injection in 5×FAD mice. b The 5×FAD mice were fed with either PLX3397 or control chow for 14 days and then injected with either sTREM2 protein or vehicle control. After continued feeding with PLX3397 or control chow for 7 days, coronal sections were stained with DAPI (blue) for nuclei, MOAB-2 (green) for Aβ, and Iba1 (red) for microglia. Representative images of the hippocampus region are shown. Original magnification ×20; scale bar, 100 μm. c Quantitation of amyloid plaque deposition in b (n = 5 mice, 18 fields of ctrl and 22 fields of PLX3397 for analysis, paired Student’s t test). d, e Brain slices from control chow (d) or PLX3397-fed (e) 5×FAD mice were incubated with 50 nM recombinant sTREM2 protein for 1 h at room temperature, and transferred to the chamber for LTP recording. Time course of fEPSP measures were recorded in the hippocampal CA1 region before and after 100-Hz stimulation in the Schaffer collateral region. Normalized fEPSP slopes were plotted every 1 min for each group. f The averaged fEPSPs recorded 50–60 min after induction of LTP (n = 10 slices for Ctrl, n = 6 slices for PLX3397, four mice per group, unpaired Student’s t test). g Synaptic proteins from the hippocampi were analyzed by Western blotting 7 days after vehicle or sTREM2 protein injection to the 5×FAD mice fed with control chow. h Quantitation of Western blots in g (n = 8 mice per group, paired Student’s t test). i Synaptic proteins from the hippocampi were analyzed by Western blotting 7 days after vehicle or sTREM2 protein injection to the 5×FAD mice fed with PLX3397. j Quantitation of Western blots in i (n = 6 mice per group, paired Student’s t test). All data are presented as mean ± SEM. *p < 0.05; **p < 0.01; ***p < 0.001; ns, not significant