EFFECTS OF SHORT-TERM PHYTOESTROGEN SUPPLEMENTATION ON THE BEHAVIOR OF MALE AND FEMALE MICE

Purpose: Plant-derived, non-steroidal compounds called phytoestrogens have been widely used as substitutes for estrogen in anticipation of estrogen-like therapeutic effects without producing the side effects associated with estrogen therapy. Human and animal data are still controversial regarding the beneficial effects of such compounds and whether they are differential based on the gender/sex of the subjects. This study investigated the effects of short-term phytoestrogen intake on the age-associated behavioral changes in the young, middle and old mice of both sex. Methods: Separate groups of young (6 months), middle (12 months) and old (24 months) male and female C57BL/6J mice were placed on either a phytoestrogen-free (PF) diet (N=15-17) or a phytoestrogen-rich (PR) diet containing (350-650 mg/kg phytoestrogens (N=16-19) for a period of 16 weeks. After 5 weeks on the diets, the mice were subjected to a series of behavioral tests to measure spontaneous activity (locomotor activity), anxiety (elevated plus maze, EPM), and cognitive function (water maze and active avoidance test). Results: PR mice exhibited increased spontaneous activity when compared to the PF mice, regardless of sex and especially in their rearing activity. In the EPM task, female mice spent less time in the open arms when compared to their males counterpart. At 24 months, PR male mice spent less time in open arms than their age-matched controls. In the water maze, PR mice performed worse than the PF mice which was particularly noticeable in the old mice, however there was no effect of the diet in the males. No major effects of diets were found in the active avoidance paradigm. Conclusions: Overall, short-term supplementation with phytoestrogens did not seem to affect anxiety levels or cognitive, though it may adversely impact spatial learning and memory in female mice, especially of old age.