Fig. 2: In vivo administration of the selective A2AR antagonist KW6002 reduces synaptic alterations and macroorchidism in Fmr1 KO mice.
A Timeline of chronic oral treatment schedule (4 mg/kg per day, PO) between 6 and 18 weeks of age. The inset shows that KW6002-chronic treatment did not affect body growth. The bodyweight increase during the 12 weeks of chronic treatment was not different between KW- and VEH-treated animals of both sexes. B The DHPG-induced LTD was strongly reduced in KO/KW mice (n = 4 animals, 8 slices, °p < 0.01 vs. KO/VEH, n = 5 animals, 8 slices, Mann-Whitney test). No difference was observed between WT/KW and WT/VEH mice (n = 2 animals, 5 slices, and n = 2 animals, 4 slices, respectively); a difference was observed between WT/VEH and KO/VEH mice (*p < 0.05, Mann-Whitney test). C The dot-plot graph summarizes the results. Insets in panel (B) show representative fEPSP recordings in correspondence of baseline (1) and late washout (3). Calibration bars: 1 mV, 10 ms. D Spine density was higher in dendrites of KO/VEH compared to WT/VEH mice (WT/VEH n = 9 and KO/VEH n = 8; *p < 0.05, Mann-Whitney test) and normalized in chronically treated KO/KW mice (n = 10, KO/KW vs. KO/VEH: °p < 0.05, Mann-Whitney test). The histograms show dendritic spines number (number of spines/dendrite segment length) counted on 5 segments per neuron in pyramidal neurons in the CA1 subfield of the hippocampus in WT and Fmr1 KO mice, VEH- or KW-treated. Bars represent mean ± SEM. Representative images of Golgi-stained sections of the dorsal hippocampus and of apical dendrite segments of CA1 hippocampal pyramidal neurons (scale bar: 25 μm) in WT and Fmr1 KO mice, VEH- or KW-treated, are reported below the graph. E KO/VEH mice (n = 7; 18 weeks of age) presented a larger testis weight compared to WT/VEH mice (n = 6; genotype effect: *p < 0.01, Mann-Whitney test), which was corrected in KO/KW mice (n = 9; treatment effect: °p < 0.05, Mann-Whitney test).
