Browsing by Subject "motor function"
Now showing 1 - 3 of 3
- Results Per Page
- Sort Options
Item Antioxidants, Exercise, APOE Genotype and Brain Function(2014-12-01) Chaudhari, Kiran; Nathalie Sumien; Michael J. Forster; Eric B. GonzalesApolipoprotein E4 (APOE4) is a well-established and extensively prevalent genetic risk factor for the development of Alzheimer’s disease (AD). The presence of APOE4 allele accelerates the pathophysiology and symptomology of AD. A large set (36%) of the population suffering from AD expresses APOE4. Being a chronic progressive disease with very few pharmaco-therapeutic agents approved by FDA, non-drug lifestyle modifications have been an important part of management of AD. People often eat healthy diet rich in antioxidants and focus on healthy living habits such as exercise. Health care providers frequently suggest combining antioxidants with physical activity for higher benefits. Antioxidants have been beneficial in counteracting oxidative stress and improving learning and memory. Similarly, different regimens of exercise also improved cognition and delayed development of AD. However, the nature of the interaction between antioxidants and exercise remain elusive and complicated. While some studies reported additive effects, others have also shown a concerning antagonistic action of the antioxidants on the beneficial effects of exercise. In the context of APOE genotype, we set our study to determine the nature of such interaction between antioxidants and exercise. Using vitamins C and E and a treadmill-based forced exercise in a genetically modified mouse model expressing human APOE3 and APOE4 (GFAP-APOE3, GFAP-APOE4), we explored the nature of that interaction on functional and biochemical outcomes. We examined the mice for spatial learning and memory, working memory and executive function, coordinated running performance, muscular reflexes, spontaneous locomotor activity, anxiety and muscle strength. Interestingly, we observed that the young adult mice expressing E4 allele performed better on higher brain functions including spatial learning and memory and short term memory in contrast to middle age mice, which developed a cognitive deficit as expected. Motor functions, reflexes and coordination were poor among all the mice carrying E4 allele irrespective of age. Antioxidants and exercise interventions led to outcomes that were dependent on genotype, age and the brain function under consideration. There was additive beneficial effect of combination of antioxidants and exercise on cognitive outcomes but not on motor outcomes in middle age groups. However, in young adults, an antagonistic interaction was observed on motor outcomes but no such interaction was observed on cognitive outcomes. Hence we can conclude that, combination of antioxidants and exercise is not a “fit for all” approach and needs to be tailored base on individual’s age and genotype.Item Dietary Curcumin And Caloric Restriction As Interventions For The Reversal Of Age Associated Functional Decline(2015-12-01) Sarker, Marjana R.; Forster, Michael J.; Franks, Susan; Sumien, NathalieAugmentation and exacerbation of oxidative stress and low-grade chronic systemic inflammation during mid-life has been proposed as modifiable causative factors for neurobehavioral decline reported with normal aging. Physiologically, the imbalance of pro-oxidants and endogenous antioxidants leads to an increase in tissue- damaging oxidative stress. Aging has also been associated with chronic systemic inflammation that can damage healthy tissues and diminish cognitive and motor capacity. The overall hypothesis of this project is that caloric restriction and dietary curcumin, via their strong anti-oxidant and anti-inflammatory properties; can delay the onset or ameliorate cognitive and motor decline in middle aged and aged mice respectively. Study 1: Fifteen month-old male C57BL/6 mice were tested as a model of sedentary mid-life obesity for the pilot study. They underwent dietary treatment for 12 weeks and were subjected to cognitive tests at the 8th week of treatment. Dietary treatments included regular chow fed ad libitum (AL), curcumin (1g/kg of diet) fed ad libitum (CURAL) and 30% to weight stable caloric restriction (CR). Mice were tested for spatial learning and cognitive flexibility testing. Blood was collected to measure inflammation and oxidative stress. Results from the pilot study indicated a significant weight loss and reduced adiposity in the CR group; whereas CURAL mice maintained stable weight throughout the treatment, consumed more food than the AL mice, and did not show a reduction of adipose tissue. However, both the CR and CURAL groups took fewer trials than AL to reach criterion during the reversal sessions of the active avoidance task, suggesting an improvement in cognitive flexibility. The AL mice had higher levels of CRP compared to CURAL and CR, and reduced glutathione as well as the GSH/GSSG ratio were increased during curcumin intake, suggesting a reducing shift in the redox state. Study 2: In the subsequent study, 15 and 20 month old female and male C57BL/6 mice were used as a normal aging model to study functional decline. This study included all of the dietary interventions from the pilot study and an additional combination diet of CR and curcumin (CURCR). Curcumin was added to the diet at 7g/kg of diet with mice under CURCR receiving 7.2g/kg of diet, adjusted to take difference in food intake into account. The mice underwent dietary treatments for 4 months, and cognitive and motor behavior tests were conducted at 8 weeks of treatment. Mice were tested on multiple tasks that are sensitive to age associated cognitive and motor dysfunction. Results from the second study indicated females to be more active than males. Mice under CR and CURCR performed better in the motor tests compared to their age matched controls, which included coordinated running, wire suspension and bridge walking. Cognitive flexibility was significantly better for middle-aged males under CR and CURAL compared to AL but not under CURCR, suggesting an antagonistic interaction. On the other hand, middle aged and aged female experimental groups did significantly better than AL. No interaction of CR and CUR was observed in aged males, with CURAL and CR yielding comparable benefits. None of the treatments had a significant effect on hippocampus- dependent rate of learning in middle age or the aged; however middle aged males under the CURCR intervention had poorer probe performance compared to their age matched controls. Data from both projects suggest that independent of weight loss; dietary curcumin and CR have positive effects on fronto-cortical functions in late middle age and senescence that could be linked to anti-inflammatory or antioxidant actions. These effects were similar across different behavioral tasks and were non-additive or antagonistic in a sex dependent manner, suggesting that they could involve the same or similar mechanisms including an influence of sex hormones. Therefore, curcumin intake may mimic the neurobehavioral outcomes of CR that could be age dependent, but the mechanism of action underlying the outcomes of the CR and curcumin combination treatments need to be further examined.Item Neurobehavioral and biochemical consequences of chronic, low-dose methamphetamine exposure in male and female mice(2022-08) Davis, Delaney L.; Sumien, Nathalie; Huang, Ren-Qi; Gatch, Michael B.; Phillips, Nicole R.; Schreihofer, Derek A.; Ma, RongAlthough prescription psychostimulants are effective in reducing attention deficit hyperactivity disorder (ADHD) symptomology, misuse of these drugs can pose serious risks such as potential abuse, dependence, and/or neurotoxicity. Of particular concern is that young adults have the highest prevalence of prescription stimulant misuse, with almost 10% of college students admitting to using amphetamine (e.g. Adderall) or methylphenidate (e.g. Ritalin) products. Despite these drugs being widely used for therapeutic and recreational use, the long-term effects of prescription stimulants have not been systematically evaluated in controlled clinical trials. Therefore, it is critical to conduct this research because young adults may be a vulnerable, at-risk population to the potential adverse consequences of long-term amphetamine use. This dissertation research evaluates the biochemical and behavioral consequences of chronic exposure of the prototypical psychostimulant, methamphetamine (METH), in a rodent model. It is hypothesized that repeated doses of METH, within the therapeutic dosing range used in a clinical setting, will induce neurotoxicity through the interplay of biological mechanisms of oxidative stress, glutamate excitotoxicity, neuroinflammation and epigenetic alterations and increase susceptibility to addiction that will be exacerbated by aging processes. Overall, the body of results showed short-term alterations in brain biochemistry and behavioral function, that do not necessarily persist past 5 months after METH treatment. In conclusion, this dissertation highlights the importance of long-term studies in addressing prescription stimulant misuse in an adult population to better understand the safety of these widely used and prescribed psychostimulants.