Figure 4

Probenecid reduces protein expression of NLRP1 inflammasome and ameliorates spatial learning deficits in aged rats. (A) Representative immunoblots of cleaved caspase-1, pannexin1 and P2X7R in hippocampal lysates of vehicle (Veh)-treated and probenecid (Pr)-treated 18-month-old rats. β-tubulin was used as an internal control. (B) Densitometric analysis of immunoblots from brain lysates of cleaved caspase-1 (Casp1), P2X7 receptor (P2X7R), and pannexin1 (PanX1). (C-D) Aged animals underwent behavioral testing following either probenecid or vehicle treatment. (C) In a hippocampal-dependent spatial learning task via Morris water maze, latency to platform was measured on days 1-3 and 8-10. Probenecid-treatment improved latency to platform measured on the final day of testing (D) Mean path length was determined on day 10 of testing and probenecid-treated rats demonstrated significantly shorter mean path lengths than vehicle-treated controls. Drug treatment was administered twice daily for 3 days (days 7-9). Data are presented as mean +/- SEM *p < 0.05, **p < 0.005 compared to vehicle. N = 6-8/per group.