Matching Items (26)
Description
After natural menopause in women, androstenedione becomes the primary hormone secreted by the residual follicle deplete ovaries. Two independent studies, in rodents that had undergone ovarian follicular depletion, found that higher serum androstenedione levels correlated with increased working memory errors. This led to the hypothesis that androstenedione impairs memory. The current study directly tested this hypothesis, examining the cognitive effects of androstenedione administration in a rodent model. Middle-aged ovariectomized rats received vehicle or one of two doses of androstenedione (4 or 8 mg/kg daily). Rats were tested on a spatial working and reference memory maze battery including the water radial arm maze, Morris maze, and delay-match-to-sample task. Results showed that androstenedione at the highest dose impaired reference memory and working memory, including ability to maintain performance as memory demand was elevated. The latter was true for both high temporal demand memory retention of one item of spatial information, as well as the ability to handle multiple items of spatial working memory information. Glutamic acid decarboxylase (GAD) levels were measured in multiple brain regions to determine whether the gamma-aminobutyric acid (GABA) system mediates androstenedione's cognitive impairments. Results showed that higher entorhinal cortex GAD levels were correlated with poorer Morris maze performance, regardless of androstenedione treatment. These findings suggest that androstenedione, the main hormone produced by the follicle deplete ovary, is detrimental to spatial learning, reference memory, and working memory, and that spatial reference memory performance might be related to the GABAergic system.
ContributorsCamp, Bryan Walter (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Olive, Michael F (Committee member) / Conrad, Cheryl D. (Committee member) / Arizona State University (Publisher)
Created2012
Description
Ethinyl estradiol, (EE) a synthetic, orally bio-available estrogen, is the most commonly prescribed form of estrogen in oral contraceptives (Shively, C., 1998), and is found in at least 30 different contraceptive formulations currently prescribed to women (Curtis et al., 2005). EE is also used in hormone therapies prescribed to menopausal women, such as FemhrtTM (Simon et al., 2003). Thus, EE is prescribed clinically to women at ages ranging from puberty through reproductive senescence. Here, in two separate studies, the cognitive effects of cyclic or tonic EE administration following ovariectomy (Ovx) were evaluated in young, female rats. Study I assessed the cognitive effects of low and high doses of EE, delivered tonically via a subcutaneous osmotic pump. Study II evaluated the cognitive effects of low, medium, and high doses of EE administered via a daily subcutaneous injection. For these studies, the low and medium doses correspond to the range of doses currently used in clinical formulations, and the high dose corresponds to the range of doses prescribed to a generation of women between 1960 and 1970, when oral contraceptives first became available. For each study, cognition was evaluated with a battery of maze tasks tapping several domains of spatial learning and memory. At the highest dose, EE treatment impaired multiple domains of spatial memory relative to vehicle treatment, regardless of administration method. When given cyclically at the low and medium doses, EE did not impact working memory, but transiently impaired reference memory during the learning phase of testing. Of the doses and regimens tested here, only EE at the highest dose impaired several domains of memory; this was seen for both cyclic and tonic regimens. Cyclic and tonic delivery of low EE, a dose that corresponds to doses used in the clinic today, resulted in transient and null impairments, respectively, on cognition.
ContributorsMennenga, Sarah E (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Baxter, Leslie C. (Committee member) / Olive, Michael F. (Committee member) / Arizona State University (Publisher)
Created2012
Description
Cognitive function declines with normal age and disease states, such as Alzheimer's disease (AD). Loss of ovarian hormones at menopause has been shown to exacerbate age-related memory decline and may be related to the increased risk of AD in women versus men. Some studies show that hormone therapy (HT) can have beneficial effects on cognition in normal aging and AD, but increasing evidence suggests that the most commonly used HT formulation is not ideal. Work in this dissertation used the surgically menopausal rat to evaluate the cognitive effects and mechanisms of progestogens proscribed to women. I also translated these questions to the clinic, evaluating whether history of HT use impacts hippocampal and entorhinal cortex volumes assessed via imaging, and cognition, in menopausal women. Further, this dissertation investigates how sex impacts responsiveness to dietary interventions in a mouse model of AD. Results indicate that the most commonly used progestogen component of HT, medroxyprogesterone acetate (MPA), impairs cognition in the middle-aged and aged surgically menopausal rat. Further, MPA is the sole hormone component of the contraceptive Depo Provera, and my research indicates that MPA administered to young-adult rats leads to long lasting cognitive impairments, evident at middle age. Natural progesterone has been gaining increasing popularity as an alternate option to MPA for HT; however, my findings suggest that progesterone also impairs cognition in the middle-aged and aged surgically menopausal rat, and that the mechanism may be through increased GABAergic activation. This dissertation identified two less commonly used progestogens, norethindrone acetate and levonorgestrel, as potential HTs that could improve cognition in the surgically menopausal rat. Parameters guiding divergent effects on cognition were discovered. In women, prior HT use was associated with larger hippocampal and entorhinal cortex volumes, as well as a modest verbal memory enhancement. Finally, in a model of AD, sex impacts responsiveness to a dietary cognitive intervention, with benefits seen in male, but not female, transgenic mice. These findings have clinical implications, especially since women are at higher risk for AD diagnosis. Together, it is my hope that this information adds to the overarching goal of optimizing cognitive aging in women.
ContributorsBraden, Brittany Blair (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Neisewander, Janet L (Committee member) / Conrad, Cheryl D. (Committee member) / Baxter, Leslie C (Committee member) / Arizona State University (Publisher)
Created2012
Description
Women are now living longer than ever before, yet the age of spontaneous menopause has remained stable. This results in an increasing realization of the need for an effective treatment of cognitive and physiological menopausal and post-menopausal symptoms. The most common estrogen component of hormone therapy, conjugated equine estrogens (CEE; Premarin) contains many estrogens that are not endogenous to the human body, and that may or may not be detrimental to cognition (Campbell and Whitehead, 1977; Engler-Chiurazzi et al., 2011; Acosta et al., 2010). We propose the use of a novel treatment option in the form of a naturally-circulating (bioidentical) estrogen called estriol. Due to estriol’s observed positive effects on synaptic functioning and neuroprotective effects in the hippocampus (Ziehn et al., 2012; Goodman et al., 1996), a brain structure important for spatial learning and memory, estriol is promising as a hormone therapy option that may attenuate menopausal- and age- related memory decline. In the current study, we administered one of the three bioidentical estrogens (17β-Estradiol, 4.0 µg/day; Estrone, 8.0 µg/day; Estriol, 8.0 µg/day) or the vehicle polyethylene glycol by subcutaneous osmotic pump to ovariectomized Fisher-344 rats. We compared these groups to each other using a battery of spatial learning tasks, including the water radial-arm maze (WRAM), Morris water maze (MM), and delayed-match-to-sample maze (DMS). We found that all estrogens impaired performance on the WRAM compared to vehicle, while 17β-estradiol administration improved overnight forgetting performance for the MM. The estriol group showed no cognitive enhancements relative to vehicle; however, there were several factors indicating that both our estriol and estradiol doses were too high, so future studies should investigate whether lower doses of estriol may be beneficial to cognition.
ContributorsStonebarger, Gail Ashley (Author) / Bimonte-Nelson, Heather (Thesis director) / Knight, George (Committee member) / Engler-Chiurrazzi, Elizabeth (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor)
Created2015-05
Description
Regional and geographical differences may explain variability in menopausal symptom occurrence due to development of climate-specific thermoneutral zones leading to population-specific hot flash frequencies. Limited information available regarding menopausal symptoms in underserved women living in extreme heat.
Understanding the perception of menopausal symptoms in underserved women living in extreme heat regions to identify if heat impacts perception of menopausal symptoms was the objective of this study. Women in free, low-income, and homeless clinics in Phoenix were surveyed during summer and winter months using a self-administered, written questionnaire including demographic, climate and menopause related questions, including the Green Climacteric Scale (GCS).
A total of 139 predominantly Hispanic (56 %), uninsured (53 %), menopausal (56 %), mid-aged (mean 49.9, SD 10.3) women were surveyed— 36% were homeless or in shelters. Most women were not on menopausal hormone therapy (98 %). Twenty-two percent reported hot flashes and 26% night sweats. Twenty-five percent of women reported previously becoming ill from heat. More women thought season influenced menopausal symptoms during summer than winter (41 % vs. 14 %, p = 0.0009). However, majority of women did not think temperature outside influenced their menopausal symptoms and that did not differ by season (73 % in winter vs. 60% in summer, p=0.1094). No statistically significant differences seen for vasomotor symptoms between winter and summer months.
Regional and geographical differences may be key in understanding the variability in menopausal symptoms. Regardless of season, the menopausal, underserved and homeless women living in Arizona reported few vasomotor symptoms. In the summer, they were more likely to report that the season influenced their menopausal symptoms rather than temperature suggesting an influence of the season on symptom perception.
ContributorsMukarram, Mahnoor (Author) / Hondula, David M. (Thesis director) / Kling, Juliana (Committee member) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Following natural menopause, androstenedione becomes the main hormone secreted by the follicle-depleted ovaries. We have previously evaluated high physiological doses of androstenedione in the female rodent, and found relations between higher androstenedione levels and spatial memory impairment; this relationship was shown when androstenedione levels were of endogenous, or exogenous, origin (Acosta et al., 2009, Camp et al., 2012). This androstenedione-induced memory impairment in females led us to question whether this androgen also impairs memory in males; no study has yet evaluated androstenedione's impact on cognition in the male rodent model. This is a clinically relevant question, as androstenedione is a steroid of abuse. In the current study, four-month old male rats were given either a daily injection of androstenedione, androstenedione with anastrozole or vehicle (polyethylene glycol). Subjects completed a battery of cognitive tasks evaluating spatial working, reference, and recent memory including the water radial arm maze (WRAM), Morris water maze (MM), and delayed match-to-sample maze (DMTS). We found that androstenedione administration impaired spatial cognitive performance in MM on early overnight forgetting and DMTS early recent memory trials across all days of testing. In addition, we found that androstenedione with anastrozole administration impaired spatial cognitive performance in the learning phases and early overnight forgetting in the MM but had no impact in DMTS testing. There were no significant differences in the WRAM maze for either group. Our findings suggest that androstenedione can impair spatial reference and early recent memory, and that anastrozole reverses this impairment for early recent memory, but not reference memory. Interpreted in the context of hormone conversion, androstenedione's effects on spatial learning and memory may be due, in part, to its conversion to estrone.
ContributorsTorres, Laura Maria (Co-author) / Camp, Bryan (Co-author) / Karber, Lily (Co-author) / Hiroi, Ryoko (Co-author, Committee member) / Bimonte-Nelson, Heather (Co-author, Thesis director) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-05
Description
Estradiol (E2) and Levonorgestrel (Levo) are two hormones commonly used in hormone therapy (HT) to decrease symptoms associated with menopause. Both of these hormones have been shown to have beneficial effects on cognition when given alone in a rodent model of menopause. However, it is unknown whether these hormones, when taken in combination, are beneficial or harmful to cognition. This is a critically important question given that these hormones are most often given in combination versus separately. This thesis is composed of two studies examining the cognitive effects of E2 and Levo using a rat model of surgical menopause. Study 1 assessed how the dose of E2 treatment in rats impacted cognitive performance, and found that low dose E2 enhanced working memory performance. Next, based on the results from Study 1, Study 2 used low dose E2 in combination with different doses of Levo to examine the cognitive effects of several E2 to Levo ratio combinations. The results from Study 2 demonstrated that the combination of low dose E2 with a high dose of Levo at a 1:2 ratio impaired cognition, and that the ratio currently used in HT, 3:1, may also negatively impact cognition. Indeed, there was a dose response effect indicating that working and reference memory performance was incrementally impaired as Levo dose increased. The findings in this thesis suggest that the E2 plus Levo combination is likely not neutral for cognitive function, and prompts further evaluation in menopausal women, as well as drug discovery research to optimize HT using highly controlled preclinical models.
ContributorsBerns-Leone, Claire Elizabeth (Co-author) / Prakapenka, Alesia (Co-author) / Pena, Veronica (Co-author) / Northup-Smith, Steven (Co-author) / Melikian, Ryan (Co-author) / Ladwig, Ducileia (Co-author) / Patel, Shruti (Co-author) / Croft, Corissa (Co-author) / Bimonte-Nelson, Heather (Thesis director) / Glenberg, Arthur (Committee member) / Conrad, Cheryl (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
Aging and the menopause transition are both intricately linked to cognitive changes
during mid-life and beyond. Clinical literature suggests the age at menopause onset can differentially impact cognitive status later in life. Yet, little is known about the relationship between behavioral and brain changes that occur during the transitional stage into the post-menopausal state. Much of the pre-clinical work evaluating an animal model of menopause involves ovariectomy in rodents; however, ovariectomy results in an abrupt loss of circulating hormones and ovarian tissue, limiting the ability to evaluate gradual follicular depletion. The 4-vinylcyclohexene diepoxide (VCD) model simulates transitional menopause in rodents by selectively depleting the immature ovarian follicle reserve and allowing animals to retain their follicle-deplete ovarian tissue, resulting in a profile similar to the majority of menopausal women. Here, Vehicle or VCD treatment was administered to ovary-intact adult and middle-aged Fischer-344 rats to assess the cognitive effects of transitional menopause via VCD-induced follicular depletion over time, as well as to understand potential interactions with age, with VCD treatment beginning at either six or twelve months of age. Results indicated that subjects that experience menopause onset at a younger age had impaired spatial working memory early in the transition to a follicle-deplete state. Moreover, in the mid- and post- menopause time points, VCD-induced follicular depletion amplified an age effect, whereby Middle-Aged VCD-treated animals had poorer spatial working and reference memory performance than Young VCD-treated animals. Correlations suggested that in middle age, animals with higher circulating estrogen levels tended to perform better on spatial memory tasks. Overall, these findings suggest that the age at menopause onset is a critical parameter to consider when evaluating learning and memory across the transition to reproductive senescence. From a translational perspective, this study informs the field with respect to how the age at menopause onset might impact cognition in menopausal women, as well as provides insight into time points to explore for the window of opportunity for hormone therapy during the menopause transition to attenuate age- and menopause- related cognitive decline, and produce healthy brain aging profiles in women who retain their ovaries throughout the lifespan.
during mid-life and beyond. Clinical literature suggests the age at menopause onset can differentially impact cognitive status later in life. Yet, little is known about the relationship between behavioral and brain changes that occur during the transitional stage into the post-menopausal state. Much of the pre-clinical work evaluating an animal model of menopause involves ovariectomy in rodents; however, ovariectomy results in an abrupt loss of circulating hormones and ovarian tissue, limiting the ability to evaluate gradual follicular depletion. The 4-vinylcyclohexene diepoxide (VCD) model simulates transitional menopause in rodents by selectively depleting the immature ovarian follicle reserve and allowing animals to retain their follicle-deplete ovarian tissue, resulting in a profile similar to the majority of menopausal women. Here, Vehicle or VCD treatment was administered to ovary-intact adult and middle-aged Fischer-344 rats to assess the cognitive effects of transitional menopause via VCD-induced follicular depletion over time, as well as to understand potential interactions with age, with VCD treatment beginning at either six or twelve months of age. Results indicated that subjects that experience menopause onset at a younger age had impaired spatial working memory early in the transition to a follicle-deplete state. Moreover, in the mid- and post- menopause time points, VCD-induced follicular depletion amplified an age effect, whereby Middle-Aged VCD-treated animals had poorer spatial working and reference memory performance than Young VCD-treated animals. Correlations suggested that in middle age, animals with higher circulating estrogen levels tended to perform better on spatial memory tasks. Overall, these findings suggest that the age at menopause onset is a critical parameter to consider when evaluating learning and memory across the transition to reproductive senescence. From a translational perspective, this study informs the field with respect to how the age at menopause onset might impact cognition in menopausal women, as well as provides insight into time points to explore for the window of opportunity for hormone therapy during the menopause transition to attenuate age- and menopause- related cognitive decline, and produce healthy brain aging profiles in women who retain their ovaries throughout the lifespan.
ContributorsKoebele, Stephanie Victoria (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Aiken, Leona S. (Committee member) / Conrad, Cheryl D. (Committee member) / Wynne, Clive DL (Committee member) / Arizona State University (Publisher)
Created2015
Description
Unmanned aerial vehicles have received increased attention in the last decade due to their versatility, as well as the availability of inexpensive sensors (e.g. GPS, IMU) for their navigation and control. Multirotor vehicles, specifically quadrotors, have formed a fast growing field in robotics, with the range of applications spanning from surveil- lance and reconnaissance to agriculture and large area mapping. Although in most applications single quadrotors are used, there is an increasing interest in architectures controlling multiple quadrotors executing a collaborative task. This thesis introduces a new concept of control involving more than one quadrotors, according to which two quadrotors can be physically coupled in mid-flight. This concept equips the quadro- tors with new capabilities, e.g. increased payload or pursuit and capturing of other quadrotors. A comprehensive simulation of the approach is built to simulate coupled quadrotors. The dynamics and modeling of the coupled system is presented together with a discussion regarding the coupling mechanism, impact modeling and additional considerations that have been investigated. Simulation results are presented for cases of static coupling as well as enemy quadrotor pursuit and capture, together with an analysis of control methodology and gain tuning. Practical implementations are introduced as results show the feasibility of this design.
ContributorsLarsson, Daniel (Author) / Artemiadis, Panagiotis (Thesis advisor) / Marvi, Hamidreza (Committee member) / Berman, Spring (Committee member) / Arizona State University (Publisher)
Created2016
Description
This study examined the relationships between the amount of physical activity engagement and two sets of health-related tests: measures of physical fitness (abdominal curl-ups, push-ups, handgrip strength, hip flexibility, and cardiorespiratory fitness) as well as measures of motor skill performance (kicking, throwing, jumping, hopping, running, and standing from a supine position) in mid-life women (ages 45-65). Physical activity engagement was assessed using 7-day accelerometer readings and the Stanford Brief Activity Survey. Motor skill performance was assessed using scores of maximum kicking, throwing, jumping, hopping, and running speeds and maximum jumping distance. Physical fitness was assessed using scores of maximum abdominal curl-ups, push-ups, handgrip strength, hip flexibility, and cardiorespiratory fitness. Results suggest that regular participation in moderate lifestyle, walking, and vigorous physical activity are related to better performances in curl-ups, push-ups, cardiorespiratory fitness on a submaximal treadmill test, kicking, throwing, and transitioning from a supine position to standing. These data represent the feasibility of selected motor skills and physical fitness tests for mid-life women and suggest that a relationship may be present between selected motor skills and health-related physical fitness measures and physical activity.
ContributorsHouse, Hannah Elizabeth (Author) / Ainsworth, Barbara (Thesis director) / Der Ananian, Cheryl (Committee member) / Stodden, David (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2013-05