Scientific Publications by FDA Staff

Horm Behav 2012 Sep;62(4):491-9

Acute genistein treatment mimics the effects of estradiol by enhancing place learning and impairing response learning in young adult female rats.

Pisani SL, Neese SL, Doerge DR, Helferich WG, Schantz SL, Korol DL

Endogenous estrogens have bidirectional effects on learning and memory, enhancing or impairing cognition depending on many variables, including the task and the memory systems that are engaged. Moderate increases in estradiol enhance hippocampus-sensitive place learning, yet impair response learning that taps dorsal striatal function. This memory modulation likely occurs via activation of estrogen receptors, resulting in altered neural function. Supplements containing estrogenic compounds from plants are widely consumed despite limited information about their effects on brain function, including learning and memory. Phytoestrogens can enter the brain and signal through estrogen receptors to affect cognition. Enhancements in spatial memory and impairments in executive function have been found following treatment with soy phytoestrogens, but no tests of actions on striatum-sensitive tasks have been made to date. The present study compared the effects of acute exposure to the isoflavone genistein with the effects of estradiol on performance in place and response learning tasks. Long-Evans rats were ovariectomized, treated with 17beta-estradiol benzoate, genistein-containing sucrose pellets, or vehicle (oil or plain sucrose pellets) for 2days prior to behavioral training. Compared to vehicle controls, estradiol treatment enhanced place learning at a low (4.5mug/kg) but not high dose (45mug/kg), indicating an inverted pattern of spatial memory facilitation. Treatment with 4.4mg of genistein over 2days also significantly enhanced place learning over vehicle controls. For the response task, treatment with estradiol impaired learning at both low and high doses; likewise, genistein treatment impaired response learning compared to rats receiving vehicle. Overall, genistein was found to mimic estradiol-induced shifts in place and response learning, facilitating hippocampus-sensitive learning and slowing striatum-sensitive learning. These results suggest signaling through estrogen receptor beta and membrane-associated estrogen receptors in learning enhancements and impairments given the preferential binding of genistein to the ERbeta subtype and affinity for GPER.