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Visual spatial memory is enhanced in female rats (but inhibited in males) by dietary soy phytoestrogens

Trent D Lund12*, Timothy W West1, Lilyan Y Tian1, Lihong H Bu1, Daniel L Simmons13, Kenneth DR Setchell4, Herman Adlercreutz5 and Edwin D Lephart1

Author Affiliations

1 The Neuroscience Center Brigham Young University, Provo, Utah 84602, USA

2 Department of Psychology Brigham Young University, Provo, Utah 84602, USA

3 Department of Chemistry and Biochemistry Brigham Young University, Provo, Utah 84602, USA

4 Clinical Mass Spectrometry Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA

5 Institute for Preventive Medicine, Nutrition, and Cancer Folkhälsan Research Center, and Division of Clinical Chemistry, Biomedicum, P.O.B. 63, University of Helsinki, Finland

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BMC Neuroscience 2001, 2:20  doi:10.1186/1471-2202-2-20

Published: 17 December 2001



In learning and memory tasks, requiring visual spatial memory (VSM), males exhibit superior performance to females (a difference attributed to the hormonal influence of estrogen). This study examined the influence of phytoestrogens (estrogen-like plant compounds) on VSM, utilizing radial arm-maze methods to examine varying aspects of memory. Additionally, brain phytoestrogen, calbindin (CALB), and cyclooxygenase-2 (COX-2) levels were determined.


Female rats receiving lifelong exposure to a high-phytoestrogen containing diet (Phyto-600) acquired the maze faster than females fed a phytoestrogen-free diet (Phyto-free); in males the opposite diet effect was identified. In a separate experiment, at 80 days-of-age, animals fed the Phyto-600 diet lifelong either remained on the Phyto-600 or were changed to the Phyto-free diet until 120 days-of-age. Following the diet change Phyto-600 females outperformed females switched to the Phyto-free diet, while in males the opposite diet effect was identified.

Furthermore, males fed the Phyto-600 diet had significantly higher phytoestrogen concentrations in a number of brain regions (frontal cortex, amygdala & cerebellum); in frontal cortex, expression of CALB (a neuroprotective calcium-binding protein) decreased while COX-2 (an inducible inflammatory factor prevalent in Alzheimer's disease) increased.


Results suggest that dietary phytoestrogens significantly sex-reversed the normal sexually dimorphic expression of VSM. Specifically, in tasks requiring the use of reference, but not working, memory, VSM was enhanced in females fed the Phyto-600 diet, whereas, in males VSM was inhibited by the same diet. These findings suggest that dietary soy derived phytoestrogens can influence learning and memory and alter the expression of proteins involved in neural protection and inflammation in rats.