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  • br Conclusion In conclusion our findings

    2019-11-04


    Conclusion In conclusion, our findings do not suggest that HT is an important determinant of future AD risk and are in line with a recent Cochrane review stating that HT is not indicated for preventing dementia or cognitive decline in postmenopausal women [13].
    Contributors
    Conflict of interest
    Funding BI is a recipient of a grant from the Finnish Cultural Foundation and funding from the Doctoral Program of Molecular Medicine, University of Eastern Finland. A-MT acknowledges funding from the Academy of Finland (grant numbers 295334 and 307232) and strategic funding from the University of Eastern Finland. HS acknowledges EU 7th FP [email protected] (Grant Nexturastat A receptor Agreement No: 601055), MIND-AD, Academy of Finland 291803 (EU Joint Programme-Neurodegenerative Disease Research) and VTR funding from MIND-AD by Kuopio University Hospital.
    Ethical approval
    Provenance and peer review
    Introduction Cyclical changes in Nexturastat A receptor and progestin levels may influence the integration of stimuli in the environment. Levels of estrogen and progestogens change over the estrous cycle, such that levels are high when female rodents are in behavioral estrous, and low when in diestrous. These hormonal changes can be associated with behavioral alterations, particularly approach, anxiety and cognitive behaviors. When rats are in behavioral estrous, approach behaviors are high while anxiety behavior is low, compared to diestrous and intact male rats (Frye et al., 2000). High progesterone levels during the luteal phase are positively correlated with motor coordination and improvement on visual, perceptual and verbal memory (Berman et al., 1997, Broverman et al., 1981, Hampson and Kimura, 1988, Hampson, 1990, Phillips and Sherwin, 1992). Progesterone improves attention, implicit memory and performance on frontal lobe tasks when levels are high (Maki et al., 2002, Solis-Ortiz et al., 2004). Rats in behavioral estrous demonstrate improved cognition in object recognition and object placement tasks (Frye et al., 2007, Walf et al., 2006). When endogenous hormone sources are removed by ovariectomy, estrogen and progestin levels are reduced and the cyclic increases in estrogen and progesterone are no longer observed (Walf et al., 2006). Administration of estrogen and/or progesterone can reinstate hormonal levels to those observed in behavioral estrous and can influence the expression of approach and avoidance behavior (Walf et al., 2006). When rodents are ovariectomized, approach behaviors toward novelty are decreased, and anxiety is increased compared to that of rats in behavioral estrous (Frye et al., 2000, Frye and Walf, 2004, Walf et al., 2006). The increase in anxiety behaviors observed in ovariectomized rats also may be due to decline in estrogen and/or progestogens. Administration of estrogen and/or progesterone increases approach toward novel stimuli and decreases fear behaviors compared to vehicle (Frye and Walf, 2004, Walf et al., 2006). Furthermore, administration of estrogen and/or progesterone to ovariectomized rats decreases anxiety behaviors in the open field and elevated plus maze tasks (Frye and Walf, 2004). Administration of progesterone to ovariectomized rats post-training increases object memory (Frye and Lacey, 2000). However, administration of high, but not physiological, dosages of progesterone attenuates estrogen\'s effects to improve spatial memory consolidation, suggesting physiological levels of progesterone do not counter estrogen\'s mediation of learning and memory (Harburger et al., 2007). These results demonstrate that motivated behaviors, such as willingness to approach novel stimuli and/or explore novel environments, occur with physiological levels of progesterone and/or estrogen. However, it is important to examine not only effects of steroid hormones on mediating positive pro-approach and anti-anxiety behaviors, but also negative avoidant and/or impulsive behaviors.