title: The effects of dietary treatment with S-equol on learning and memory processes in middle-aged ovariectomized rats.
abstract: 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 0mg (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.
authors.affiliation: Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, 2001S. Lincoln Avenue, Urbana, IL 61802, USA; Neuroscience Program, University of Illinois at Urbana-Champaign, 505 South Goodwin Avenue, Urbana, IL 61801, USA; Department of Psychology and Neuroscience, Baldwin Wallace University, 275 Eastland Road, Berea, OH 44017, USA. Electronic address: stlneese@illinois.edu.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Neese
authors.affiliation: Neuroscience Program, University of Illinois at Urbana-Champaign, 505 South Goodwin Avenue, Urbana, IL 61801, USA. Electronic address: spisan2@illinois.edu.
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Pisani
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079-9502, USA. Electronic address: daniel.doerge@fda.hhs.org.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Doerge
authors.affiliation: Department of Food Science and Human Nutrition, University of Illinois at Urbana-Champaign, 905S Goodwin Avenue, Urbana, IL 61801, USA. Electronic address: helferic@illinois.edu.
authors.forename: William G
authors.initials: WG
authors.lastname: Helferich
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079-9502, USA. Electronic address: estatira.sepehr@fda.hhs.gov.
authors.forename: Estatira
authors.initials: E
authors.lastname: Sepehr
authors.affiliation: National Center for Natural Product Research, University of Mississippi, 3011 Thad Cochran Research Center, University, MS 38677, USA. Electronic address: amar@olemiss.edu.
authors.forename: Amar G
authors.initials: AG
authors.lastname: Chittiboyina
authors.affiliation: National Center for Natural Product Research, University of Mississippi, 3011 Thad Cochran Research Center, University, MS 38677, USA. Electronic address: sckumarr@olemiss.edu.
authors.forename: Sateesh Chandra Kumar
authors.initials: SC
authors.lastname: Rotte
authors.affiliation: National Center for Natural Product Research, University of Mississippi, 3011 Thad Cochran Research Center, University, MS 38677, USA. Electronic address: tsmillie@olemiss.edu.
authors.forename: Troy J
authors.initials: TJ
authors.lastname: Smillie
authors.affiliation: National Center for Natural Product Research, University of Mississippi, 3011 Thad Cochran Research Center, University, MS 38677, USA. Electronic address: ikhan@olemiss.edu.
authors.forename: Ikhlas A
authors.initials: IA
authors.lastname: Khan
authors.affiliation: Neuroscience Program, University of Illinois at Urbana-Champaign, 505 South Goodwin Avenue, Urbana, IL 61801, USA; Department of Biology, Syracuse University, 107 College Place, Syracuse, NY 13244, USA. Electronic address: dlkorol@syr.edu.
authors.forename: Donna L
authors.initials: DL
authors.lastname: Korol
authors.affiliation: Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, 2001S. Lincoln Avenue, Urbana, IL 61802, USA; Neuroscience Program, University of Illinois at Urbana-Champaign, 505 South Goodwin Avenue, Urbana, IL 61801, USA. Electronic address: schantz@illinois.edu.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Schantz
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D060754:Equol / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D019833:Genistein / Q000633:toxicity; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000178:diet therapy*; D008570:Memory, Short-Term; D010052:Ovariectomy; D048789:Phytoestrogens / Q000633:toxicity; D051381:Rats; D020318:Rats, Long-Evans; D030262:Soybean Proteins / Q000008:administration & dosage
chemical_list: D048789:Phytoestrogens; D030262:Soybean Proteins; D060754:Equol; D019833:Genistein
keywords: Aging; Equol; Executive function; Phytoestrogens; Place learning