Browsing by Author "Vann, Phillip"
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Item Catwalk analysis: a novel approach to profiling age differences in gait(2016-03-23) Wong, Jessica; Vann, Phillip; Forster, Michael; Sumien, Nathalie; Mock, J.The Catwalk is a validated video-based gait analysis tool for quantitative analysis of both static and dynamic differences in rodent gait and weight-bearing. The Catwalk has been used to analyze disease states such as stroke, sciatic nerve crush and osteoarthritis, however age-related changes in rodent gait are not well characterized. Motor impairments have been associated with dysregulated cellular redox state, namely levels of reduced to oxidized glutathione. Glutamate-cysteine ligase modifier (gclm) is a key enzyme sub-unit in the production of glutathione (GSH), and knocking it out reduces GSH levels by 85%. The gclm -/- mice are a potential model of accelerated aging and should develop impairments earlier than wild-type mice. Our hypothesis was that gait measures would decrease with advanced age and that impairments would occur sooner in gclm -/- mice. Wild-type (wt) and gclm-/- male and female mice were tested at 4, 10 or 17 months of age (n = 8-11/group). All testing was done in pitch black and a camera below the illuminated transparent platform captured each paw print as animals walked across the platform. Paw prints were automatically labeled according to left/right or front/hind then manually checked. A criterion for a good run was set as less than 60% speed variation within the run and less than 10% speed variation between runs. Two to five runs per animal were used for two-way analyses of variance of the dependent measures collected using Genotype and Age as in between factors. The dependent measures were gait speed (SP), front and hind base of support (BoSf, BoSh), front and hind stride length (SLf, SLh), front and hind stride speed (SSf, SSh), front and hind step cycle (SCf, SCh), and front and hind duty cycle (DCf, DCh). Gait speed decreased with age in both genotypes. BoS decreased in front legs and increased in hind legs in both genotypes. Stride length was decreased with age, and more prominently in the gclm-/-, while stride speed decreased with age and was higher in gclm-/-. Step cycles increased with age in the wt but not in the gclm-/-. Duty cycles increased with age, especially in the gclm-/-. These preliminary data suggest that age leads to measurable changes in mouse gait and that GSH dysregulation had only minor effects on gait. In conclusion, Catwalk analysis is sufficiently sensitive to measure subtle age-related changes in gait across several age-ranges, and can be added to the current battery of behavioral tests.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 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 presentationItem Sexual Dimorphism in Mouse Age-Related Motor Impairments(2017-03-14) Wong, Jessica; Vann, Phillip; Davis, Delaney; Forster, Michael; Sumien, Nathalie; Mock, J.Purpose: Clinical measures such as frailty, disability, and strength loss are correlated with decreased survival and are more prevalent in women, yet men have a higher mortality risk at all ages. This contradictory sexual dimorphism in mortality versus morbidity is not fully understood. Furthermore, many pre-clinical studies using rodents have combined sexes or tested only males which limits the possible inferences regarding sex-dependent changes in function across the lifespan as well as inferences relating to interventions. Therefore, the purpose of this study was to examine murine sexual dimorphism in age-related motor function decline. Our hypothesis was that motor impairments would increase with age, and that these deficiencies would be exacerbated in females. Methods: Male and female C57BL/6J mice were tested at 5, 10, and 20 months of age. Animals underwent a battery of behavioral tests measuring difference aspects of motor function, including tests measuring coordinated running and motor learning (rotorod), strength (wire suspension), and balance (bridge walking). Resulting dependent measures were analyzed using two-way analyses of variance with Age and Sex as between-groups factors and two-way repeated measures analyses of variance with Session as the within group factor. Results: Rotorod performance (learning and maximum) declined with age in both sexes, however declines were smaller for females at 10 and 20 months compared to the males. Latency to fall from the wire was significantly shorter in adult and old males compared to their young counterpart, while there was no significant differences in the females. Bridge walking performance declined in both males and females, but there was a larger decline in the males. Furthermore, age-related decline in balance was observed in the females only on the most difficult bridge, while age-related declines were apparent on all the bridges for the males. Conclusions: These data support that age-related decline leads to measurable changes in mouse motor function. However these deficits occur primarily in the males whereas females displayed fewer and smaller declines in motor function. This suggests that combining sexes or testing only a single sex could lead to limited results. Interestingly, women are typically more sensitive to age-related functional decline, while female mice in our study were less affected by age-related decline. In conclusion, this study highlights the importance of including both sexes in rodent pre-clinical research.