Direct hippocampal infusion of methylene blue by mini-osmotic pump reverses spatial navigation related learning and memory deficits by reducing tau levels in rTg4510 mice. (A) Four groups of wildtype mice (n = 3) were injected with 100 μM MB, 1 mM MB, or saline into the hippocampus for 24 hours. Western blot from hippocampal lysates show reductions in tau at 1 mM MB in phospho- and total tau. (B) Experimental design of central administration of MB (MB central n = 6, saline central n = 7). (C) Infusion of MB increased ability of rTg4510 mice to learn the location of the hidden platform in the MWM, **p < 0.01). (D) Probe trial of Morris water maze shows that MB treated rTg4510 mice were able to recognize the target from the opposite quadrant, unlike saline treated rTg4510 mice, (F(3,20) = 8.202, p = 0.0009), ***p < 0.001. (E) Number of crossing across the area where the hidden platform was located during training. (F(7, 44) = 2.757, p = 0.0183), p < 0.05. (F) Search strategy imaging using a camera tracking system shows that MB treated rTg4510 mice have a more focused strategy than saline treated rTg4510 mice.