Figure 9.

Compound 11 treatment rescues cognitive deficits and cortex size in tau transgenic animal model. (A) Compound 11 treatment of rTg4510 mice (white triangles) results in a reduction in errors in the RAWM cognitive function assay compared to vehicle-treated rTg4510 animals (gray squares). Outcomes for compound 11 treated mice are comparable to disease state control mice (black circles; doxy-treated rTg4510 mice). (B) Contextual fear conditioning shows that compound 11 treatment (white bar) rescues the freezing deficit seen in rTg4510 mice treated with vehicle (gray bar), reaching levels similar to the control doxy-treated rTg4510 animals (black bar). (C) Vehicle-treated rTg4510 mice (gray bar) show reduced cerebral cortex size compared to control doxy-treated mice (black bar), and compound 11 treatment of rTg4510 mice (white bar) prevents the cortical tissue loss (t test: p < 0.05 vs Tg4510 vehicle). (D) Reductions in hippocampal size also manifest in the rTg4510 mice (gray bar) compared to the doxy mice (black bar). Compound 11 treatment of the rTg4510 mice (white bar) shows a trend toward rescuing the size deficit but does not reach statistical significance (p = 0.104 comparing compound 11-treated rTg4510 mice vs vehicle treated rTg4510 mice).