Fig. 7
AAV-mediated sTREM2 expression rescues behavioral and LTP deficits in 5×FAD mice. a, b Neonatal WT mice were injected with either control AAV or AAV-sTREM2 in the cerebral ventricles and analyzed after 7 months for sTREM2 expression at the mRNA (a, n = 6 mice for Ctrl in hippo or cortex, n = 6 mice for sTREM2 in hippo and n = 5 mice for sTREM2 in the cortex, unpaired Student’s t test) or protein (b, n = 6 mice per group, unpaired Student’s t test) levels in the cortex and hippcampus using RT-qPCR or ELISA, respectively. c–e Morris water maze tests were performed in wild-type (WT) or 5×FAD mice 6 months after injection of either control AAV or AAV-sTREM2 (n = 12 mice for WT-Ctrl, n = 19 mice for WT-sTREM2, n = 11 mice for 5×FAD-Ctrl, and n = 10 mice for 5×FAD-sTREM2, two-way ANOVA, Bonferonni post hoc analyses). The escape latency time to reach the hidden platform was recorded during the 7-day training (c). Probe trial was performed 24 h after the last trial of a hidden platform task and the percentage of search time for each quadrant was recorded (d). Swimming speed of each group was recorded during the probe trial (e). f Time course of fEPSP measures recorded in the hippocampal CA1 region before and after 100-Hz stimulation in the Schaffer collateral region in slices from WT or 5×FAD mice 7 months after receiving control AAV or AAV-sTREM2. Normalized fEPSP slopes were plotted every 1 min for each group. g The averaged fEPSPs recorded 50–60 min after induction of LTP (n = 8 slices for WT-Ctrl, n = 10 slices for WT-sTREM2, n = 6 slices for 5×FAD-Ctrl, and n = 8 slices for 5×FAD-sTREM2, at least three mice per group, two-way ANOVA, Bonferonni post hoc analyses). All data are presented as mean ± SEM. *p < 0.05; **p < 0.01; ***p < 0.001; ns, not significant
