Matching Items (4)
Description
Each year, millions of aging women will experience menopause, a transition from reproductive capability to reproductive senescence. In women, this transition is characterized by depleted ovarian follicles, declines in levels of sex hormones, and a dysregulation of gonadotrophin feedback loops. Consequently, menopause is accompanied by hot flashes, urogenital atrophy, cognitive decline, and other symptoms that reduce quality of life. To ameliorate these negative consequences, estrogen-containing hormone therapy is prescribed. Findings from clinical and pre-clinical research studies suggest that menopausal hormone therapies can benefit memory and associated neural substrates. However, findings are variable, with some studies reporting null or even detrimental cognitive and neurobiological effects of these therapies. Thus, at present, treatment options for optimal cognitive and brain health outcomes in menopausal women are limited. As such, elucidating factors that influence the cognitive and neurobiological effects of menopausal hormone therapy represents an important need relevant to every aging woman. To this end, work in this dissertation has supported the hypothesis that multiple factors, including post-treatment circulating estrogen levels, experimental handling, type of estrogen treatment, and estrogen receptor activity, can impact the realization of cognitive benefits with Premarin hormone therapy. We found that the dose-dependent working memory benefits of subcutaneous Premarin administration were potentially regulated by the ratios of circulating estrogens present following treatment (Chapter 2). When we administered Premarin orally, it impaired memory (Chapter 3). Follow-up studies revealed that this impairment was likely due to the handling associated with treatment administration and the task difficulty of the memory measurement used (Chapters 3 and 4). Further, we demonstrated that the unique cognitive impacts of estrogens that become increased in circulation following Premarin treatments, such as estrone (Chapter 5), and their interactions with the estrogen receptors (Chapter 6), may influence the realization of hormone therapy-induced cognitive benefits. Future directions include assessing the mnemonic effects of: 1) individual biologically relevant estrogens and 2) clinically-used bioidentical hormone therapy combinations of estrogens. Taken together, information gathered from these studies can inform the development of novel hormone therapies in which these parameters are optimized.
ContributorsEngler-Chiurazzi, Elizabeth (Author) / Bimonte-Nelson, Heather A. (Thesis advisor) / Sanabria, Federico (Committee member) / Olive, Michael F (Committee member) / Hoffman, Steven (Committee member) / Arizona State University (Publisher)
Created2013
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
Sports related concussions, or mild traumatic brain injuries (mTBI), have recently increased in prevalence, and thus gained a great deal of recognition from the public and the media. While the acute symptoms associated with concussions are well known, which include headaches, dizziness, vomiting, and fatigue, recent research has indicated that there can be severe chronic consequences of multiple conditions. Most notably, a disease called Chronic Traumatic Encephalopathy (CTE) has been linked to multiple mTBIs, which produces symptoms similar to Alzheimer's disease and dementia, in addition to personality changes, increased suicidality, and in some cases death. This knowledge has led the NFL to take steps to protect their players, and increase both the understanding and awareness of the problems associated with multiple concussions. This comes with many problems, however, as players and fans alike are quick to resist any type of change to the rules or policies present in football, in fear that it may damage the integrity of the game. The NFL is thus forced into a difficult position, and must balance public opinion and player safety. There are things that can be done, however, that do not threaten the game itself, such as investing in concussion research and safety equipment design that will more effectively protect the brain from concussions.
ContributorsAiello, Mimi Elizabeth (Author) / Olive, M. Foster (Thesis director) / Bimonte-Nelson, Heather (Committee member) / Camp, Bryan (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor)
Created2013-05
Description
We constructed an 11-arm, walk-through, human radial-arm maze (HRAM) as a translational instrument to compare existing methodology in the areas of rodent and human learning and memory research. The HRAM, utilized here, serves as an intermediary test between the classic rat radial-arm maze (RAM) and standard human neuropsychological and cognitive tests. We show that the HRAM is a useful instrument to examine working memory ability, explore the relationships between rodent and human memory and cognition models, and evaluate factors that contribute to human navigational ability. One-hundred-and-fifty-seven participants were tested on the HRAM, and scores were compared to performance on a standard cognitive battery focused on episodic memory, working memory capacity, and visuospatial ability. We found that errors on the HRAM increased as working memory demand became elevated, similar to the pattern typically seen in rodents, and that for this task, performance appears similar to Miller's classic description of a processing-inclusive human working memory capacity of 7 ± 2 items. Regression analysis revealed that measures of working memory capacity and visuospatial ability accounted for a large proportion of variance in HRAM scores, while measures of episodic memory and general intelligence did not serve as significant predictors of HRAM performance. We present the HRAM as a novel instrument for measuring navigational behavior in humans, as is traditionally done in basic science studies evaluating rodent learning and memory, thus providing a useful tool to help connect and translate between human and rodent models of cognitive functioning.
ContributorsMennenga, Sarah (Author) / Baxter, Leslie C. (Author) / Grunfeld, Itamar (Author) / Brewer, Gene (Author) / Aiken, Leona (Author) / Engler-Chiurazzi, Elizabeth (Author) / Camp, Bryan (Author) / Acosta, Jazmin (Author) / Braden, B. Blair (Author) / Schaefer, Keley (Author) / Gerson, Julia (Author) / Lavery, Courtney (Author) / Tsang, Candy (Author) / Hewitt, Lauren (Author) / Kingston, Melissa L. (Author) / Koebele, Stephanie (Author) / Patten, Kristopher (Author) / Ball, B. Hunter (Author) / McBeath, Michael (Author) / Bimonte-Nelson, Heather (Author) / College of Liberal Arts and Sciences (Contributor)
Created2014-09-09