Effects of long-term dietary administration of estrogen receptor-beta agonist diarylpropionitrile on ovariectomized female ICR (CD-1) mice
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.
KeywordsEstrogen receptor beta Diarylpropionitrile Aging Lifespan Frailty Anxiety
This work was supported in part by a Natural Sciences and Engineering Research Council of Canada Discovery Grant to JAS.
Compliance with ethical standards
All procedures were approved by the Animal Care and Use Committee at Brock University, in compliance with CCAC guidelines.
- Bains RS, Cater HL, Sillito RR, Chartsias A, Sneddon D, Concas D, Keskivali-Bond P, Lukins TC, Wells S, Acevedo Arozena A, Nolan PM, Armstrong JD (2016) Analysis of individual mouse activity in group housed animals of different inbred strains using a novel automated home cage analysis system. Behav Neurosci 10:1–12Google Scholar
- Bean LA, Ianov L, Foster TC (2014) Estrogen Receptors, the Hippocampus, and Memory. Neuroscientist 20(5):534–545Google Scholar
- Han SK, Lee D, Lee H, Kim D, Son HG, Yang J-S, Lee S-J V, Kim S (2016) OASIS 2: online application for survival analysis 2 with features for the analysis of maximal lifespan and healthspan in aging research. Oncotarget 7(35):56147–56152Google Scholar
- Jacome LF, Gautreaux C, Inagaki T, Mohan G, Alves S, Lubbers LS, Luine V (2010) Estradiol and ERÎ² agonists enhance recognition memory, and DPN, an ERÎ² agonist, alters brain monoamines. Neurobiol Learn Mem 94(4):488–498Google Scholar
- Mancuso M, Leonardi S, Giardullo P, Pasquali E, Borra F, Stefano ID, Prisco MG, Tanori M, Scambia G, Majo VD, Pazzaglia S, Saran A, Gallo D (2011) The estrogen receptor beta agonist diarylpropionitrile (DPN) inhibits medulloblastoma development via anti-proliferative and pro-apoptotic pathways. Cancer Lett 308:197–202CrossRefPubMedGoogle Scholar
- Rosenfeld CS, Ferguson SA (2014) Barnes maze testing strategies with small and large rodent models. J Vis Expt 84:e51194Google Scholar
- Strong R, Miller RA, Antebi A, Astle CM, Bogue M, Denzel MS, Fernandez E, Flurkey K, Hamilton KL, Lamming DW, Javors MA, de Magalhaes JP, Martinez PA, McCord JM, Miller BF, Muller M, Nelson JF, Ndukum J, Rainger GE, Richardson A, Sabatini DM, Salmon AB, Simpkins JW, Steegenga WT, Nadon NL, Harrison DE (2016) Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α-glucosidase inhibitor or a Nrf2-inducer. Aging Cell 15:872–884CrossRefPubMedPubMedCentralGoogle Scholar