Figure 3.

Neuronal overexpression of A_2AR favours spatial memory deficits in THY-Tau22 transgenic mice. Effects of neuronal overexpression of A_2AR on spontaneous activity, anxiety-like behaviour, spatial learning and memory of THY-Tau22 mice. (A and B) No change of either spontaneous locomotion or velocity was observed using actimetry. (C) Anxiety-like behaviour evaluated using elevated plus maze. Double transgenic mice overexpressing A_2AR performed as wild-type controls. As expected, tau transgenic mice spent more time in the open arms, a change similarly observed in triple tau/A_2AR transgenic mice. ^***P < 0.001 versus wild-type mice using one-way ANOVA followed by Tukey’s post hoc test. (D) Evaluation of the spatial learning using the Barnes maze task revealed that all groups of animals learned the position of the escape box in a time-dependent manner during the four days of training. (E) During the probe test, while displaying a preference, A_2AR mice spent significantly less time in the target quadrant (T) than wild-type controls. At the early age tested (5–6 months old), tau transgenic mice did not exhibit significant memory impairments with a strong preference for the target quadrant. In contrast, triple tau/A_2AR mice did not show preference for the target quadrant (T) over the other quadrants (O), supporting significant spatial memory deficits. ^$P < 0.05 versus wild-type mice; °P < 0.05, °°P < 0.01, °°°P < 0.001 versus Target quadrant using one-way ANOVA followed by Tukey’s post hoc test. (F) In agreement, the latency to reach the target hole was significantly increased for tau/A_2AR mice as compared to the other experimental groups. °°P < 0.01 versus wild-type mice using one-way ANOVA followed by Tukey’s post hoc test. n = 7–22 per group. Results are expressed as mean ± SEM.