Figure 3.

Adora2a antagonism restores BBB integrity and rescues synaptic plasticity in mice with diet-induced insulin resistance. A, Increases in hippocampal NaFl extravasation were eliminated by treatment with the Adora2a antagonist SCH58261 or vehicle (Veh) in mice maintained on LFD or HFD for 16 weeks. B, Visualization of NaFl and Evans blue on hippocampal sections. Scale bar: (in LFD/Veh) for all micrographs, 200 μm. C, Increased hippocampal penetration of Evans blue was blocked by SCH58261 in mice with diet-induced insulin resistance. A, C, Bar height represents the average of (n = 8–12) mice per condition. D, Adora2a antagonist treatment normalizes dentate gyrus long-term potentiation in hippocampal slices from HFD mice. Bar graph (right) shows percentage increase in field EPSP (fEPSP) slope during minutes 50–60 of recording. E, Bath application of SCH58261 has no effect on LTP deficits in slices from vehicle-treated HFD mice. D, E, Bars or symbol height represents the average of (n = 9–14) slices from each condition. For traces in D and E, scale bars: (bottom right) y-axis, 1.0 mV; x-axis, 10 ms. For all graphs, error bars represent SEM and asterisk (*) indicates significance at p < 0.05 by ANOVA with Bonferroni's post hoc.