Document Detail

Impact of dietary genistein and aging on executive function in rats.
MedLine Citation:
PMID:  19945528     Owner:  NLM     Status:  MEDLINE    
Genistein is an estrogenic soy isoflavone widely promoted for healthy aging, but its effects on cognitive function are not well-understood. We examined the cognitive effects of once daily oral genistein treatment at two doses (approximately 162 microg/kg/day low dose and a 323 microg/kg/day high dose) in ovariectomized young (7 month), middle-aged (16 month), and old (22 month) Long-Evans rats. Operant tasks including delayed spatial alternation (DSA), differential reinforcement of low rates of responding (DRL), and reversal learning that tap prefrontal cortical function were used to assess working memory, inhibitory control/timing, and strategy shifting, respectively. At the conclusion of cognitive testing, brains were collected and relative densities of D1 and D2 dopamine receptors and dopamine transporter (DAT) were measured in the prefrontal cortex. On the DSA task, the high dose old group performed worse than both the high dose young and middle-aged groups. On the DRL task, the high dose of genistein resulted in a marginally significant impairment in the ratio of reinforced to non-reinforced lever presses. This effect was present across age groups. Age effects were also found as old rats performed more poorly than the young and middle-aged rats on the DSA overall. In contrast, middle-aged and old rats made fewer lever presses on the DRL than did the young rats, a pattern of behavior associated with better performance on this task. Moreover, while DAT levels overall decreased with age, genistein treatment produced an increase in DAT expression in old rats relative to similarly aged control rats. D1 and D2 densities did not differ between genistein dose groups or by age. These results highlight the fact that aspects of executive function are differentially sensitive to both genistein exposure and aging and suggest that altered prefrontal dopamine function could potentially play a role in mediating these effects.
Steven L Neese; Victor C Wang; Daniel R Doerge; Kellie A Woodling; Juan E Andrade; William G Helferich; Donna L Korol; Susan L Schantz
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2009-11-27
Journal Detail:
Title:  Neurotoxicology and teratology     Volume:  32     ISSN:  1872-9738     ISO Abbreviation:  Neurotoxicol Teratol     Publication Date:    2010 Mar-Apr
Date Detail:
Created Date:  2010-03-15     Completed Date:  2010-06-15     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  8709538     Medline TA:  Neurotoxicol Teratol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  200-11     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2009 Elsevier Inc. All rights reserved.
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MeSH Terms
Aging / physiology*
Brain Chemistry / drug effects
Cognition Disorders / chemically induced*,  physiopathology
Disability Evaluation
Dopamine / metabolism
Dose-Response Relationship, Drug
Executive Function / drug effects*,  physiology
Food, Formulated / adverse effects
Genistein / toxicity*
Memory, Short-Term / drug effects,  physiology
Neuropsychological Tests
Neurotoxicity Syndromes / physiopathology
Phytoestrogens / toxicity
Prefrontal Cortex / drug effects*,  metabolism,  physiopathology
Rats, Long-Evans
Receptors, Dopamine / drug effects,  metabolism
Grant Support
P01 AG024387/AG/NIA NIH HHS; P01 AG024387/AG/NIA NIH HHS; P01 AG024387-010003/AG/NIA NIH HHS; T32 ES007326/ES/NIEHS NIH HHS; T32 ES007326/ES/NIEHS NIH HHS; T32 ES007326-09/ES/NIEHS NIH HHS
Reg. No./Substance:
0/Phytoestrogens; 0/Receptors, Dopamine; DH2M523P0H/Genistein; VTD58H1Z2X/Dopamine

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