TY - JOUR
T1 - The effects of dietary treatment with S-equol on learning and memory processes in middle-aged ovariectomized rats
AU - Neese, Steven L.
AU - Pisani, Samantha L.
AU - Doerge, Daniel R.
AU - Helferich, William G.
AU - Sepehr, Estatira
AU - Chittiboyina, Amar G.
AU - Rotte, Sateesh Chandra Kumar
AU - Smillie, Troy J.
AU - Khan, Ikhlas A.
AU - Korol, Donna L.
AU - Schantz, Susan L.
N1 - Funding Information:
The authors would like to thank Mindy Howe and Suren Bandara for their help with OVX surgeries and daily animal care and John Katzenellebogen for reviewing this manuscript. This research was supported by the P50 AT006268 from ODS , NCAAM , and NCI (DLK, SLS, DRD, WGH). Steven Neese also received support from the National Institute of Environmental Health Sciences Grant T32 ES007326 .
PY - 2014/1
Y1 - 2014/1
N2 - The use of over-the-counter botanical estrogens containing isolated soy isoflavones, including genistein and daidzein, has become a popular alternative to traditional hormone therapies. Menopausal women use these products as an aide in healthy aging, including for the maintenance of cognitive function. The safety and efficacy of many of these commercial preparations remain unknown. Previous research in our lab found that treatment of ovariectomized (OVX) female Long-Evans rats with genistein impaired working memory in an operant delayed spatial alternation (DSA) task and response learning in a plus-maze, but enhanced place learning assessed in the plus-maze. The present study further examined the effects of isolated isoflavones on working memory and place learning by treating middle-aged (12-13. month old) OVX female Long-Evans rats with S-equol, the exclusive enantiomer produced by metabolism of daidzein in the mammalian gut. S-equol binds selectively to ERβ with an affinity similar to that of genistein but has low transcriptional potency. For DSA testing, S-equol at 1.94, 0.97. mg, or 0. mg (sucrose control) was orally administered to animals daily, 30. min before behavioral testing, and again both 4 and 8. hours after the first treatment. Rats were tested on the DSA task following the first, morning dose. For place learning, rats received 0.97. mg. S-equol every 4. hours during the light portion of the cycle beginning 48. hours prior to behavioral testing (total exposure 8.7. mg. S-equol). S-equol treatment was largely without effect on the DSA and place learning tasks. This is the first study to test the behavioral effects of isolated S-equol in OVX rodents, and shows that, unlike genistein or estradiol, repeated daily treatment with this isoflavone metabolite does not alter learning and memory processes in middle-aged OVX rats.
AB - The use of over-the-counter botanical estrogens containing isolated soy isoflavones, including genistein and daidzein, has become a popular alternative to traditional hormone therapies. Menopausal women use these products as an aide in healthy aging, including for the maintenance of cognitive function. The safety and efficacy of many of these commercial preparations remain unknown. Previous research in our lab found that treatment of ovariectomized (OVX) female Long-Evans rats with genistein impaired working memory in an operant delayed spatial alternation (DSA) task and response learning in a plus-maze, but enhanced place learning assessed in the plus-maze. The present study further examined the effects of isolated isoflavones on working memory and place learning by treating middle-aged (12-13. month old) OVX female Long-Evans rats with S-equol, the exclusive enantiomer produced by metabolism of daidzein in the mammalian gut. S-equol binds selectively to ERβ with an affinity similar to that of genistein but has low transcriptional potency. For DSA testing, S-equol at 1.94, 0.97. mg, or 0. mg (sucrose control) was orally administered to animals daily, 30. min before behavioral testing, and again both 4 and 8. hours after the first treatment. Rats were tested on the DSA task following the first, morning dose. For place learning, rats received 0.97. mg. S-equol every 4. hours during the light portion of the cycle beginning 48. hours prior to behavioral testing (total exposure 8.7. mg. S-equol). S-equol treatment was largely without effect on the DSA and place learning tasks. This is the first study to test the behavioral effects of isolated S-equol in OVX rodents, and shows that, unlike genistein or estradiol, repeated daily treatment with this isoflavone metabolite does not alter learning and memory processes in middle-aged OVX rats.
KW - Aging
KW - Equol
KW - Executive function
KW - Phytoestrogens
KW - Place learning
UR - http://www.scopus.com/inward/record.url?scp=84893153319&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84893153319&partnerID=8YFLogxK
U2 - 10.1016/j.ntt.2013.12.004
DO - 10.1016/j.ntt.2013.12.004
M3 - Article
C2 - 24368316
AN - SCOPUS:84893153319
SN - 0892-0362
VL - 41
SP - 80
EP - 88
JO - Neurotoxicology and Teratology
JF - Neurotoxicology and Teratology
ER -