BDNF and Alzheimer disease: Notably, although phosphatidylinositol 3-kinase (PI3K) have also been implicated in BDNF signaling, their activation is not required for spatial memory recovery in our AD model rats because the PI3K inhibitor wortmannin could not block the beneficial effect of hippocampal BDNF on long term memory restore in the Aβ1-42-injected rats (data not shown).