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- All Subjects: Cognition
- All Subjects: Dogs
- All Subjects: Tumor Suppressor Genes
- Creators: Bimonte-Nelson, Heather
- Creators: Tollis, Marc
Description
Due to artificial selection, dogs have high levels of phenotypic diversity, yet, there appears to be low genetic diversity within individual breeds. Through their domestication from wolves, dogs have gone through a series of population bottlenecks, which has resulted in a reduction in genetic diversity, with a large amount of linkage disequilibrium and the persistence of deleterious mutations. This has led to an increased susceptibility to a multitude of diseases, including cancer. To study the effects of artificial selection and life history characteristics on the risk of cancer mortality, we collected cancer mortality data from four studies as well as the percent of heterozygosity, body size, lifespan and breed group for 201 dog breeds. We also collected specific types of cancer breeds were susceptible to and compared the dog cancer mortality patterns to the patterns observed in other mammals. We found a relationship between cancer mortality rate and heterozygosity, body size, lifespan as well as breed group. Higher levels of heterozygosity were also associated with longer lifespan. These results indicate larger breeds, such as Irish Water Spaniels, Flat-coated Retrievers and Bernese Mountain Dogs, are more susceptible to cancer, with lower heterozygosity and lifespan. These breeds are also more susceptible to sarcomas, as opposed to carcinomas in smaller breeds, such as Miniature Pinschers, Chihuahuas, and Pekingese. Other mammals show that larger and long-lived animals have decreased cancer mortality, however, within dog breeds, the opposite relationship is observed. These relationships could be due to the trade-off between cellular maintenance and growing fast and large, with higher expression of growth factors, such as IGF-1. This study further demonstrates the relationships between cancer mortality, heterozygosity, and life history traits and exhibits dogs as an important model organism for understanding the relationship between genetics and health.
ContributorsBalsley, Cassandra Sierra (Author) / Maley, Carlo (Thesis director) / Wynne, Clive (Committee member) / Tollis, Marc (Committee member) / School of Life Sciences (Contributor) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
Description
Urbanization exposes wildlife to many unfamiliar environmental conditions, including the presence of novel structures and food sources. Adapting to or thriving within such anthropogenic modifications may involve cognitive skills, whereby animals come to solve novel problems while navigating, foraging, etc. The increased presence of humans in urban areas is an additional environmental challenge that may potentially impact cognitive performance in wildlife. To date, there has been little experimental investigation into how human disturbance affects problem solving in animals from urban and rural areas. Urban animals may show superior cognitive performance in the face of human disturbance, due to familiarity with benign human presence, or rural animals may show greater cognitive performance in response to the heightened stress of unfamiliar human presence. Here, I studied the relationship between human disturbance, urbanization, and the ability to solve a novel foraging problem in wild-caught juvenile house finches (Haemorhous mexicanus). This songbird is a successful urban dweller and native to the deserts of the southwestern United States. In captivity, finches captured from both urban and rural populations were presented with a novel foraging task (sliding a lid covering their typical food dish) and then exposed to regular periods of high or low human disturbance over several weeks before they were again presented with the task. I found that rural birds exposed to frequent human disturbance showed reduced task performance compared to human-disturbed urban finches. This result is consistent with the hypothesis that acclimation to human presence protects urban birds from reduced cognition, unlike rural birds. Some behaviors related to solving the problem (e.g. pecking at and eying the dish) also differed between urban and rural finches, possibly indicating that urban birds were less neophobic and more exploratory than rural ones. However, these results were unclear. Overall, these findings suggest that urbanization and acclimation to human presence can strongly predict avian response to novelty and cognitive challenges.
ContributorsCook, Meghan Olivia (Author) / McGraw, Kevin (Thesis director) / Bimonte-Nelson, Heather (Committee member) / Weaver, Melinda (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Brief memory tasks for use with pet dogs were developed using radial arm maze performance as a standard comparison measurement of memory capacity. Healthy pet dogs were first tested in a radial arm maze, where more errors made in completing the maze indicated poorer memory. These dogs were later tested with five novel memory tests, three of which utilized a treat placed behind a box with an identical distracter nearby. The treat placement was shown to each dog, and a 35 second delay, a 15 second delay with occluder, or a 15 second delay with room exit was observed before the dog could approach and find the treat. It was found that errors on the delayed match to sample (35 second delay) and occluder/object permanence (15 second delay with occluder) tasks were significantly positively correlated with the average number of errors made in the 8th trial of the radial arm maze (r =.58, p<.01** and r =.49, p<.05*, respectively) indicating that these new brief tests can reliably be used to assess memory in pet dogs.
ContributorsBoileau, Rae Nicole (Author) / Wynne, Clive (Thesis director) / Knight, George (Committee member) / Bimonte-Nelson, Heather (Committee member) / Barrett, The Honors College (Contributor) / Department of Psychology (Contributor)
Created2015-05
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
Menopause is reproductive senescence characterized by a loss of ovarian estrogen and progesterone. Women can experience cognitive decline and other negative symptoms with the loss of ovarian hormones (Sherwin, 2006). While hormone therapies (HT) can treat symptoms of menopause and may have neuroprotective properties, such as the potential to decrease the risk of Alzheimer's Disease (Behl & Manthey, 2000), there are many effects of current HTs that are not ideal. Indeed, optimizing conventional HTs has proven complex, indicating a need for alternative therapies. Phytoestrogens are estrogenic compounds found naturally in plants such as soybeans, that could provide new treatment options. Dietary phytoestrogens can benefit memory in the rodent model (Luine, 2006), although the mechanism underlying these effects is unclear. Basal forebrain cholinergic projections have been shown to mediate the cognitive benefits of estrogen (Gibbs, 2010); we hypothesize that phytoestrogens act similarly, via the cholinergic system, to impact memory. We administered varying doses of phytoestrogen-containing diets to ovariectomized female rats, and used the place recognition task to evaluate spatial memory. Brains were then analyzed for choline acetyltransferase (ChAT), the synthesizing enzyme for acetylcholine, in the vertical-diagonal bands (VDB) and the medial septum (MS) of the basal forebrain. Results showed that ChAT cell counts in the VDB were marginally higher with dietary phytoestrogen treatment. Further, VDB ChAT cell counts positively correlated with place recognition performance, indicating that animals with more VDB ChAT neurons exhibited better spatial memory performance. These results suggest that phytoestrogens might act similarly to natural, endogenously circulating estrogens, and identify phytoestrogens as a direction for investigation as a HT.
ContributorsMousa, Abeer Abdul (Author) / Bimonte-Nelson, Heather (Thesis director) / Olive, Foster (Committee member) / Deviche, Pierre (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / W. P. Carey School of Business (Contributor) / School of Life Sciences (Contributor) / School for the Science of Health Care Delivery (Contributor)
Created2014-05
Description
Drospirenone (DRSP) is a novel, pharmacologically unique synthetic progestin with properties more similar to the endogenous progestogen, progesterone, than any other progestin currently on the market. While a significant amount of research has been conducted on the risks associated with DRSP, the impact of DRSP on cognition, especially in reference to learning and memory, is not well understood. However, it is imperative to fully understand the cognitive effects of DRSP, both alone and in combination with EE (as taken in a combined oral contraceptive [COC]), so that women and their physicians can make a fully-informed decision when deciding to take a DRSP-containing COC. Study 1 examined the effects of three doses of DRSP in order to determine the optimal dose for combining with EE, and found that the medium dose of DRSP (30 µg/day) enhanced spatial working memory performance. In Study 2, the medium dose of DRSP from Study 1 was combined with low (0.125 µg/day) and high (0.3 µg/day) doses of EE to examine the effects of DRSP as taken with EE in a COC. The results from Study 2 indicated that when DRSP was combined with a low, but not high, dose of EE, spatial working memory impairments were seen at the highest working memory load. Anxiety-like behavior was evaluated using the OFT, and DRSP was shown to decrease measures of anxiety-like behavior. Additionally, while treatment with a high dose of EE decreased several measures of anxiety-like behavior, a low dose of EE did not, suggestive of a dose response. Taken together, the findings presented from both studies suggest that some of the cognitive effects of the combination of DRSP with EE are different than those of either hormone administered on its own. Further exploration in a preclinical, ovary-intact animal model is a next step to fully understand these effects in the translational context of a contraceptive, given that women taking an EE-DRSP combination are typically ovary-intact.
ContributorsPoisson, Mallori Louise (Author) / Bimonte-Nelson, Heather (Thesis director) / Doane, Leah (Committee member) / School of Nutrition and Health Promotion (Contributor) / School of Molecular Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
Bats (order Chiroptera) are the longest lived mammals for their size, with particularly extreme longevity evolving in the family Vespertilionidae, or vesper bats. Because of this, researchers have proposed using bats to study ageing and cancer suppression. Here, we study gene duplications across mammalian genomes and show that, similar to previous findings in elephants, bats have experienced duplications of the tumor suppressor gene TP53, including five genomic copies in the genome of the little brown bat (Myotis lucifugus) and two copies in Brandt's bat (Myotis brandtii). These species can live 37 and 41 years, respectively, despite having an adult body mass of only ~7 grams. We use evolutionary genetics and next generation sequencing approaches to show that positive selection has acted on the TP53 locus across bats, and two recently duplicated TP53 gene copies in the little brown bat are both highly conserved and expressed, suggesting they are functional. We also report an extraordinary genomic copy number expansion of the tumor suppressor gene FBXO31 in the common ancestor of vesper bats which accelerated in the Myotis lineage, leading to 34\u201457 copies and the expression of 20 functional FBXO31 homologs in Brandt's bat. As FBXO31 directs the degradation of MDM2, which is a negative regulator of TP53, we suggest that increased expression of both FBXO31 and TP53 may be related to an enhanced DNA-damage response to genotoxic stress brought on by long lifespans and rapid metabolic rates in bats.
ContributorsSchneider-Utaka, Aika Kunigunda (Author) / Maley, Carlo (Thesis director) / Wilson Sayres, Melissa (Committee member) / Tollis, Marc (Committee member) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
The aim of this study was to determine whether IUD administration, with and without the presence of Levo, and with and without the presence of the ovaries, impacts cognition in a rat model. Rats received either Sham or Ovariectomy (Ovx) surgery (removal of the ovaries), plus either no IUD, a Blank IUD (without Levo), or a Levo-releasing IUD (Levo IUD), enabling us to evaluate the effects of Ovx and the effects of IUD administration on cognition. Two weeks after surgery, all treatment groups were tested on the water radial arm maze, Morris water maze, and visible platform task to evaluate cognition. At sacrifice, upon investigation of the uteri, it was determined that some of the IUDs were no longer present in animals from these groups: Sham\u2014Blank IUD, Ovx\u2014Blank IUD, and Sham\u2014Levo IUD. Results from the remaining three groups showed that compared to Sham animals with no IUDs, Ovx animals with no IUDs had marginally impaired working memory performance, and that Ovx animals with Levo IUDs as compared to Ovx animals with no IUDs had marginally enhanced memory performance, not specific to a particular memory type. Results also showed that Ovx animals with Levo IUDs had qualitatively more cells in their vaginal smears and increased uterine horn weight compared to Ovx animals with no IUDs, suggesting local stimulation of the Levo IUDs to the uterine horns. Overall, these results provide alternative evidence to the hypothesis that the Levo IUD administers Levo in solely a localized manner, and suggests that the possibility for the Levo IUD to affect reproductive cyclicity in ovary-intact animals is not rejected. The potential for the Levo IUD to exert effects on cognition suggests that either the hormone does in fact systemically circulate, or that the Levo IUD administration affects cognition by altering an as yet undetermined hormonal or other feedback between the uterus and the brain.
ContributorsStrouse, Isabel Martha (Author) / Bimonte-Nelson, Heather (Thesis director) / Glenberg, Arthur (Committee member) / Sirianni, Rachael (Committee member) / Conrad, Cheryl (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description
Alzheimer's disease affects a large number of Americans every year, and research on the causes and possible prevention continues to increase. Alzheimer's disease is a form of dementia that causes problems with memory, thinking, and behavior and is thought to be caused by beta-amyloid plaques that form in the brain. In recent years, dogs have been used more and more as an animal model looking at Alzheimer's disease and cognitive dysfunction. Dogs serve as a reliable animal model because effected dogs naturally form the same beta-amyloid plaques that affected humans do as they age. Previous research has shown that older dogs perform worse on various memory tasks than do younger dogs, however researchers have struggled to find a test for dog cognitive dysfunction that is brief and can be performed in the home. The current study aimed to find a brief memory task that requires few materials, but is still reliable. The results of this study do not support the hypothesis that older dogs would perform worse than younger dogs if tested to find a treat with varying time delays of 15, 30, and 45 seconds. The results of this experiment showed a main effect of age (F = 8.40, d.f. 1, 19, p < 0.01) and delay (F = 15.14, d.f. 2, 30, p < 0.01), but age-delay interaction was not significant (F = 2.53, d.f. 2, 30, p = 0.09). Future studies should be performed using a larger sample size and this same protocol to attempt to raise the participation level of the dogs.
ContributorsZimmerman, Megan Renee (Author) / Wynne, Clive (Thesis director) / Bimonte-Nelson, Heather (Committee member) / Department of Psychology (Contributor) / W. P. Carey School of Business (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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