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Effects of long-term dietary administration of estrogen receptor-beta agonist diarylpropionitrile on ovariectomized female ICR (CD-1) mice

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Abstract

Diarylpropionitrile (DPN) is an estrogen receptor-β-specific agonist that has been linked to neuroprotection, preserving cognitive function with age, the suppression of anxiety-like behaviors, inhibition of cancer growth, and other positive properties. We hypothesized that DPN may have pro-longevity properties. DPN was administered via feed at a dose corresponding to approximately 3 mg/kg/day to ovariectomized female mice beginning at 7 months of age. Mice were followed for the duration of their lifespans while monitoring body mass, aspects of behavior, learning, memory, and frailty. DPN-treated mice gained more body mass over the first 2 years of age (17 months of the study). A test of voluntary running behavior at 24 months of age behavior revealed no deficits in DPN-treated mice, which were as likely as control mice to engage in extended bouts of wheel running, and did so at higher average speeds. DPN administration had anxiolytic-like effects when measured using an elevated plus maze at 9 months of age. A mouse frailty index was used to assess age-related changes. The correlation between age and frailty differed between control and DPN-treated mice. Overall, dietary DPN administration had some beneficial effects on the aging phenotype of ovariectomized female mice with few significant detrimental effects.

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Funding

This work was supported in part by a Natural Sciences and Engineering Research Council of Canada Discovery Grant to JAS.

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Authors and Affiliations

  1. Department of Biological Sciences, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, ON, L2S 3A1, Canada

    Sherry A. Said, Rachel Isedowo, Christilynn Guerin, Navreek N. Nar, Leesa Lillie, Shawn Bukovac, Cheryl M. McCormick & Jeffrey A. Stuart

  2. Department of Psychology, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, ON, L2S 3A1, Canada

    Shawn Bukovac, Jonathan J. Simone, Matthew R. Green & Cheryl M. McCormick

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  1. Sherry A. Said
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  2. Rachel Isedowo
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  3. Christilynn Guerin
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  4. Navreek N. Nar
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  5. Leesa Lillie
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  6. Shawn Bukovac
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  7. Jonathan J. Simone
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  8. Matthew R. Green
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  9. Cheryl M. McCormick
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  10. Jeffrey A. Stuart
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Correspondence to Jeffrey A. Stuart.

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All procedures were approved by the Animal Care and Use Committee at Brock University, in compliance with CCAC guidelines.

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Said, S.A., Isedowo, R., Guerin, C. et al. Effects of long-term dietary administration of estrogen receptor-beta agonist diarylpropionitrile on ovariectomized female ICR (CD-1) mice. GeroScience 40, 393–403 (2018). https://doi.org/10.1007/s11357-018-0038-7

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  • DOI: https://doi.org/10.1007/s11357-018-0038-7

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