Neuroscience
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12503/21662
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Browsing Neuroscience by Author "Davis, Delaney"
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Item Hormone treatments reverse stroke-associated declines in cognitive function in a rat model of menopause(2018-03-14) Davis, Delaney; Li, Wenjun; Liu, Ran; Winters, Ali; Forster, Michael; Yang, Shaohua; Sumien, Nathalie; Vann, PhillipPurpose This study addresses the critical questions important to the future of hormone therapy. The purpose of this study was to provide information on how different durations of hormone deprivation can alter the responsiveness of the brain to ischemic injuries and hormonal therapies. Ultimately, these studies will identify a window of opportunity for treatment with hormones preventing brain dysfunction associated with menopause. Methods Eighty-two Sprague-Dawley retired breeder females rats were ovariectomized (ovx). Twelve or two weeks post-surgery, the rats were implanted with hormone pellets containing cholesterol (vehicle), estrogen (E2) or progesterone (P4), which were replaced every 2 weeks. Two weeks post implantation, the rats received either a sham or ischemic stroke (transient Middle Cerebral Artery Occlusion) surgery. After a one week recovery period, the rats were subjected to a behavioral battery of tests measuring affective (plus maze), motor (rotorod) and cognitive (Morris water maze) function. The rats were then euthanized and brain regions were collected for further biochemical analyses. Data were analyzed using 2- or 3-way ANOVAs followed by pairwise comparisons. Results Treatment with E2 or P4 decreased the time spent in the open arms in both 2 and 12 weeks post-ovx groups. There was no effect of stroke or hormone treatment on the rotorod. For spatial learning and memory, stroke impaired the rats in their ability to learn and retain the location of the platform and impairments were worst in the 12-weeks post-ovx group. E2 and P4 treatment improved performance of the stroke rats in both 2 and 12-weeks post-ovx groups. Conclusions These data suggest that the outcome of stroke is worst as a function of time post-ovx, especially on spatial learning and memory. Hormonal treatment with E2 and P4 were successful in reversing the deleterious effects of stroke on cognitive function. Further studies to identify the mechanisms underlying these observations are underway.Item Influence of exogenous oxidative stress on the resilience of aged glutathione-deficient mice(2018-03-14) Sumien, Nathalie; Mock, J.; Davis, DelaneyInfluence of exogenous oxidative stress on the resilience of aged glutathione-deficient mice Delaney L. Davis, J. Thomas Mock and Nathalie Sumien Introduction With age, individuals become less resilient against stressors, rendering them more susceptible to diseases and leading to exacerbated brain impairments. Aging also involves a shift in redox state that can be associated with the key molecule, glutathione. To determine the importance of glutathione in stress resilience, we sought to study the effect of an oxidative stressor (paraquat) in an animal model of chronic glutathione deficiency. Glutathione deficiency can be achieved by the genetic knockout of the modifier subunit of the enzyme, glutamate cysteine ligase (gclm). Our hypothesis was that chronic glutathione deficiency will render mice less resilient to the oxidative stress induced by paraquat and will cause further impairments in motor and cognitive function. Methods Old (18 months) male and female gclm+/+ and gclm-/- mice received one to two intraperitoneal injections of 10 mg/kg of paraquat (PQ) or saline for one week. Four days following the last injection, animals underwent behavioral tests measuring affective, cognitive and motor function (locomotor activity, elevated zero maze, bridge walking, wire suspension, fear conditioning, rotorod, and active avoidance). After the completion of behavioral testing, brain regions, skeletal muscle, liver, heart, and kidney tissues were harvested and will be used to examine biochemical changes in oxidative damage and redox signaling. The data were analyzed using 2 or 3-way ANOVAs followed by pairwise comparisons. Results Body weights in male and female mice dropped immediately after PQ injection, with the gclm-/-treatment group having a greater decrease in percentage of body weight than the gclm+/+. PQ injections appeared to decrease overall activity of both gclm+/+ and gclm -/-. PQ-treated mice seemed to spend less time in open arms, indicating increased anxiety levels. Overall, PQ-treated mice appeared to perform better on motor skills and worse on cognitive tests. Conclusions These preliminary data suggest a trend that paraquat may have differential effects depending on the task (cognitive vs. motor), and gclm -/- mice may be more susceptible to an oxidative stressor.Item Life on the Catwalk – Age and redox state effects on mouse gait(2018-03-14) Knight, Sherilynn; Vann, Phillip; Wong, Jessica; Davis, Delaney; Forster, Michael; Sumien, Nathalie; Mock, J.1. Purpose Human clinical research has determined that changes in gait speed can be predictive of other impairments and can help identify at-risk individuals for further declines. However, age-related gait changes are not well defined in rodents, even though they are used as the primary pre-clinical model for a multitudes of diseases and for aging research. The purpose of our study was to measure age-related differences in gait, using an automated system, the CatWalk™ XT. Furthermore, age-related functional declines have been associated with a decrease in the reduced to oxidized glutathione ratio leading to a pro-oxidizing cellular shift. Using a model of chronic glutathione deficiency, we sought to determine whether redox state was a key factor in age-related gait impairments. Our hypothesis was that gait declines observed with aging would be exacerbated in glutathione-depleted mice. 2. Methods Groups of wild-type (gclm+/+) and knock-out (gclm-/-) mice aged 4, 10 and 17 months were tested on the CatWalk and gait measurements were recorded. Resulting dependent measures including gait speed, front and hind base of support, front and hind stride length, front and hind stride speed, front and hind step cycle, and front and hind duty cycle were analyzed using two-way analyses of variance with Age and Genotype as between-groups factors, followed by pairwise comparisons. 3. Results Age-related declines were observed in all aforementioned measures of gait, and chronic glutathione depletion was unexpectedly associated with delays in age-related declines for some of the measures. 4. Conclusions The CatWalk is a useful and sensitive tool to assess gait changes with age in rodents, and further studies will be required to identify the potential compensating mechanisms underlying the effects observed with the chronic glutathione depletion. Research Area Neuroscience Presentation Type Oral presentation