The Effects of Insulin-Induced Moderate Hypoglycemia on Hippocampal Plasticity

Self-regulation of blood glucose in diabetics via insulin administration introduces the risk of hypoglycemia. Previous studies have shown hypoglycemia damages the dentate gyrus, an area of the hippocampus associated with anxiety- and depressive-like behavior. To date, only depressive-like behaviors have been observed following moderate hypoglycemia. This study sought to examine whether acute moderate hypoglycemia induces both behaviors due to high clinical comorbidity. One episode of moderate hypoglycemia was induced in a male Sprague-Dawley rat. Twenty-four hours later, hippocampal function was evaluated via the elevated plus maze and the forced swim test to assess anxiety-like and depressive-like behavior. Results, though not statistically significant, suggested that acute moderate hypoglycemia may increase anxiety- and depressive-like behavior. These findings may elucidate hypoglycemia-related behavioral changes.

Effects of Wingwall Configurations on the Behavior of Integral Abutment Bridges

This research includes parametric studies performed with the use of three-dimensional nonlinear finite element models in order to investigate the effects of cantilever wingwall configurations on the behavior of integral abutment bridges located on straight alignment and zero skew. The parametric studies include all three types of cantilever wingwalls; inline, flared, and U-shaped wingwalls. Bridges analyzed vary in length from 100 to 1200 feet. Soil-structure and soil-pile interaction are included in the analysis. Loadings include dead load in combination with temperature loads in both rising and falling temperatures. Plasticity in the integral abutment piles is investigated by means of nonlinear plasticity models. Cracking in the abutments and stresses in the reinforcing steel are investigated by means of nonlinear concrete models. The effects of wingwall configurations are assessed in terms of stresses in the integral abutment piles, cracking in the abutment walls, stresses in the reinforcing steel of abutment walls, and axial forces induced in the steel girders. The models developed are analyzed for three types of soil behind the abutments and wingwalls; dense sand, medium dense sand, and loose sand. In addition, the models consider both the case of presence and absence of predrilled holes at the top nine feet of piles. The soil around the piles below the predrilled holes consists of very stiff clay. The results indicate that for the stresses in the piles, the critical load is temperature contraction and the most critical parameter is the use of predrilled holes. However, for both the stresses in the reinforcing steel and the axial forces induced in the girders, the critical load is temperature expansion and the critical parameter is the bridge length. In addition, the results indicate that the use of cantilever wingwalls in integral abutment bridges results in an increase in the magnitude of axial forces in the steel girders during temperature expansion and generation of pile plasticity at shorter bridge lengths compared to bridges built without cantilever wingwalls.

Influence of Acute and Chronic Exercise on Markers of Hippocampal Plasticity

Exercise and physical activity are lifestyle behaviors associated with enriched mental health. Understanding the mechanisms by which exercise and physical activity improve mental health may provide insight for novel therapeutic approaches for numerous mental health disorders. This dissertation reports the findings from three studies investigating the influence of acute and chronic exercise on behavioral and mechanistic markers of hippocampal plasticity and delves into the potential role of noradrenergic signaling in the hippocampal adaptations with exercise. The first study assessed the effects of long-term voluntary wheel running on hippocampal expression of plasticity-associated genes and proteins in adult male and female C57BL/6J mice, highlighting sex differences in the adaptations to long-term voluntary wheel running. The second study examined the influence of acute exercise intensity on AMPA receptor phosphorylation, a mechanism essential for hippocampal plasticity, plasticity- associated gene expression, spatial learning and memory, and anxiety-like behavior. The unexpected finding that acute exercise increased anxiety-like behavior encouraged investigation into the role of central noradrenergic signaling in acute exercise-induced anxiety. The third study determined how previous exposure to voluntary wheel running modulates the response to an acute bout of exercise, focusing primarily on transcription of the important plasticity-promoting gene, brain-derived neurotrophic factor. Using a pharmacological approach to compromise the locus coeruleus noradrenergic system, a system that is implicated in age-related mental health disorders such as Alzheimer’s Disease, the third study also investigated the influence and interaction of the noradrenergic system and acute exercise on expression of multiple brain-derived neurotrophic factor transcripts. Together, this dissertation reports the findings from a series of experiments that explored similarities, differences, and interactions between the effects of acute and chronic exercise on markers of hippocampal plasticity and behavior. Further, this work provides insight into the role of the noradrenergic system in exercise-induced hippocampal plasticity.