EFFECTS OF POSTNATAL EXPOSURE TO GENISTEIN ON ANXIETY BEHAVIOR OF CD1 MICE

Genistein is a compound belonging to the family of phytoestrogens, produced by Leguminosae and particularly abundant in soybeans. This molecule is a tyrosine kinase inhibitor and shares structural features with the 17β-estradiol so it can bind estrogen receptors, with a high affinity for ERβ than ERα, exerting both estrogenic and antiestrogenic activity. In plants it shows an antimicrobial activity, specifically to protect them against insects. Genistein, as other phytoestrogens, is largely present in human and laboratory animal diets. Phytoestrogens have recently gained recognition for their beneficial effects on human health, but little is known about the effects on brain circuitries: experiments carried out on rats feeded with phytoestrogen-rich diet have shown contrasting results on behavior and related brain areas. To understand if exposure to genistein during the postnatal critical period of differentiation of brain circuits and behaviors may alter this process, we orally administered to male and female mice from 1 postnatal day from 8 post natal day a dose of genistein (50 mg/kg in sesame oil), a dose of estradiol ( 50μg/kg in sesame oil) or only vehicle. Mice were tested postnatal day 60 and one week later they were sacrified for neurohistological investigations. Two tests were applied for anxiety behavior, the Elevated Plus Maze and the Open Field. Statistical analysis reported significant effects in the open field test for female mice (genisteins vs estradiol), whereas we have not evidenced significant effects for the Elevated Plus Maze test. In particular, genistein female mice show lower level of anxiety, in comparison to estradiol-treated, spending more time and covering more distance in center of the Open Field compared with time spent and distance covered on the periphery. These preliminary results indicate that postnatal exposure to genistein during the critical period of brain differentiation has an organizational effect on anxiety behavior in female mice. These results could be interpreted by the differential affinity of genistein and estradiol to bind ERβ and ERα. In future immunohistochemical analyses we will investigate if some neural circuits have been permanently affected. These results are partly in contrast with those obtained in a previous experiment, when genistein was administered to the pregnant females during gestation and early lactation. In that experiment we observed also a decrease of anxiety, but only in males and only in during the Elevated Plus Maze test. However, previous and present results suggest, in this murine model, that perinatal exposure to genistein may have life-long effects on differentiation of brain structures and behaviors.