P2Y1R inhibition increases the morphological barrier function of periplaque hippocampal astrocytes. (A) The mean intensity of hippocampal plaques was increased in MRS2179-treated versus vehicle-treated (Veh) APPPS1 mice, indicating greater compaction of plaques induced by the drug (n = 5 mice for each group; age of both groups, 11 mo; *, P < 0.05, Mann–Whitney test). (B–E) The number and terminal points of near-plaque astrocyte branches and the length of astrocyte segments were increased by the drug treatment, and there was a trend toward more complex astrocytic structures around plaques (*, P < 0.05, Mann–Whitney test for all comparisons; mean ± SEM). (F–I) No significant changes in these parameters were seen in periplaque microglia (P > 0.05, Mann–Whitney test for all comparisons). (J and K) Representative examples. Astrocytes were labeled with anti-GFAP antibodies, microglia were labeled with anti-Iba1 antibodies, and plaques were labeled with methoxy-X04. Bars, 30 µm.