Browsing by Author "Sumien, Nathalie PhD"
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Item Behavioral profiling of aged glutathione-deficient mice exposed to an oxidative stressor(2019-03-05) Sumien, Nathalie PhD; Davis, DelaneyPurpose Aging is associated with a decrease in brain function and vitality, along with an increased risk to stressors. Oxidative stress is a mechanism associated with aging, in which antioxidant defenses are overcome by the production of reactive oxygen species, leading to molecular damage and decreased cellular efficiency. Glutathione is a major antioxidant and indicator of cellular redox status, however its role in resilience remains unclear. To determine its involvement, we used the oxidative stressor paraquat (N,N′-dimethyl-4,4′-bipyridinium dichloride; PQ), a widely used herbicide that is highly toxic to animals and humans, in a mouse model of glutathione deficiency. The purpose of this study was to determine if paraquat-induced oxidative stress would exacerbate age-associated functional impairments in glutathione deficient mice. Methods Groups of old (18 months) male and female gclm+/+ and gclm-/- mice were assigned to a control group (saline) or a paraquat group (10 mg/kg; once via i.p.). One week following the injection, animals underwent behavioral testing of motor, affective and cognitive function (bridge walking, wire suspension, coordinated running, locomotor activity, elevated zero maze, fear conditioning, and active avoidance). Results Gclm-/- exhibited less anxious behavior than the gclm+/+, and PQ had no effect on that measure. Gclm-/- were more active than the gclm+/+, and PQ reduced that activity especially in females. PQ treatment seemed to improve cognitive flexibility, and improved associative learning in males only. PQ improved balance and strength of the gclm-/- in females, but worsened the strength in gclm+/+ males. Conclusion Overall, this study indicates that PQ did not exacerbate any phenotype associated with glutathione deficiency, and in some instances, it made the mice better. These outcomes do not support an involvement of glutathione in resiliency, however its life-long deficiency may have led to upregulation of other protective mechanisms making the mice stronger in adverse situations.Item Repetitive Mild Traumatic Brain Injury in a Mouse Model(2016-03-23) Schreihofer, Derek PhD, MS, BS; Sumien, Nathalie PhD; Khan, NabeelRepetitive mild traumatic brain injury has become a hot topic of academic and clinical research due to the neurological dysfunction in many retired pro athletes who have suffered such injuries. In this study, we evaluated a mouse model that simulates such injuries and analyzed cognitive and motor function post injury. The results were then correlated with histological findings. A weight drop model was used to induce repetitive mild head injuries in isoflurane anesthetized C57/BL6 male mice. Mice (n=7) were placed on a breakable foil platform over a sponge landing pad. A 43 gram steel weight was dropped through a guide tube from 28 inches onto the dorsal surface midline of the closed skull between the ears and eyes. Following the impact, the foil platform breaks allowing the mouse to experience rotational acceleration and land on the sponge pad. A single injury was performed daily M-F and again the following M-T (a total of 7 hits over 9 days). A group of sham injury mice (n=5) were anesthetized but did not receive TBI. Following injury, mice underwent behavioral testing for motor function, anxiety and cognitive to assess the effects of the repeated injury. Consistent with other studies of TBI in mice, animals with injury showed hyperactivity. Results showed that the mice with TBI showed significant (p The injury pattern in mice was designed to simulate the injury experience by repetitive concussion in athletes of all sports. The successful development of this model will allow future examination of pharmacological approaches to reduce mild repetitive head injury.