Short Communication Dietary phytoestrogens enhance spatial memory and spine density in the hippocampus and prefrontal cortex of ovariectomized rats V. Luine a, ⁎ , S. Attalla a , G. Mohan a , A. Costa b , M. Frankfurt c a Department of Psychology, Hunter College of CUNY, 695 Park Ave., New York, NY 10021, USA b Weill Medical School of Cornell University, New York, NY 10021, USA c Department of Physiology/Pharmacology, CUNY Medical School, New York, NY 10031, USA ARTICLE INFO ABSTRACT Article history: Accepted 6 July 2006 Available online 1 September 2006 Long-term maintenance of ovariectomized rats (9weeks) on chow containing high phytoestrogen levels (Purina LabDiet® 5001) as compared to chow with minimal phytoestrogens (Harlan 2016 Teklad) was associated with better performance of the spatial memory task, object placement, increased dendritic spine density in CA1 and prefrontal cortex pyramidal neurons, and higher uterine weights. Object recognition memory, anxiety on an elevated plus maze and body weight were unaffected by phytoestrogen levels in the diet. © 2006 Elsevier B.V. All rights reserved. Keywords: Hippocampus Phytoestrogen Prefrontal cortex Recognition memory Spatial memory A number of recent studies show that phytoestrogens exert physiological effects in rats and humans (see Lephart et al. (2002) and Lephart et al. (2005) for review). Phytoestrogens are similar in structure to estradiol and are found in some vegetables, whole grains, soy and clover products (Patisol, 2005). Depending on the physiological state of the subject and the specific phytoestrogen, these compounds may act as estrogenic agonists or antagonists, but their potency is much lower than estradiol (MacLusky, 1997). Animal feeds, including rodent chows, generally derive protein from alfalfa and soybean meal which are rich in isoflavones and coumestans, two of the more potent phytoestrogens (Lephart et al., 2002). Thus, it is possible that dietary phytoestrogens might influ- ence estrogen-sensitive neural and physiological systems. Indeed, Lephart and colleagues and others have compared rats receiving high phytoestrogen chow and phytoestrogen-free chow and found some differences in brain morphology and behavior (Lephart et al., 2002, 2005; Patisol, 2005; Perez-Martin et al., 2005). In this study, we compared ovariectomized (OVX) rats that consumed the widely used, standard rodent chow, Purina LabDiet® 5001 with those that consumed Harlan 2016 Teklad Global 16% Protein Rodent Diet chow. Purina LabDiet chow contains approximately 810 μg/g of phytoestrogens, derived mainly from soymeal (Brown and Setchell, 2001) while the 2016 Teklad chow contains no soy or alfalfa, and therefore contains minimal phytoestrogens, but is not phytoestrogen free (see http://www.teklab.com). We investigated whether behavioral, physiological and neural properties, which are known to be influenced by estradiol, would be affected in OVX rats that chronically ingested diets differing in phytoestrogen levels. Levels of dietary phytoestrogens might be an important factor to consider in experiments which investigate long-term effects of estrogens. BRAIN RESEARCH 1126 (2006) 183 – 187 ⁎ Corresponding author. Fax: +1 212 772 5620. E-mail address: vluine@hunter.cuny.edu (V. Luine). 0006-8993/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2006.07.016 available at www.sciencedirect.com www.elsevier.com/locate/brainres