Date of Award
2022
Document Type
Honors Thesis (Open Access)
Department
Colby College. Biology Dept.
Advisor(s)
Melissa Glenn
Second Advisor
Tariq Ahmad
Third Advisor
Lynn Hannum
Abstract
Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder that affects over 5 million individuals in the United States alone. While AD is primarily thought of as a disease that destroys neural networks required for memory recall and formation, AD also cause impairment in emotional regulation, cognitive flexibility, and executive function pathways. The cause of AD is unknown; however, the allele ApoE4 has been identified as a risk factor for the onset of AD. ApoE4 provides a valuable opportunity to study AD through animal models. This thesis utilized a human ApoE4 transgenic rat model (hApoE4) to investigate the biological and behavioral consequences of this AD risk allele. Cellular stress, hippocampal regulation, and behavioral tests evaluating rat cognitive function were analyzed. Cellular stress was assessed through the quantification of a novel biomarker, Growth Differentiation Factor-15 (GDF-15). Hippocampal regulation was examined in the context of neurogenesis occurrence (Doublecortin) and GABAergic neuron prevalence (Parvalbumin). It was revealed that GDF-15 serum concentrations significantly increase with age in wildtype and ApoE4 male rats, but not in ApoE4 female rats. In addition, ApoE4 males demonstrated a trend towards a reduction in PVB+ interneurons. These findings were correlated with behavioral testing data. Correlational analysis suggested the investigated biomarkers were associated with the cognitive function of hApoE4 rats, as evaluated through behavioral tests. Of most significance, this paper provides evidence suggesting the ApoE4 allele functions in a sex-dependent manner in rats, and directly alters GDF-15 levels in a potentially neurodestructive manor in female ApoE4 rats.
Keywords
Alzheimer’s Disease, Differentiation Factor-15 (GDF-15), Parvalbumin (PVB), Transgenic rat model hApoE4, Neuroscience
Recommended Citation
Schulman, Anne A., "Characterizing Cellular Stress, Hippocampal Function, and Behavior in a Novel Rat Model of Alzheimer's Disease" (2022). Honors Theses. Paper 1369.https://digitalcommons.colby.edu/honorstheses/1369
Included in
Biological Psychology Commons, Biology Commons, Nervous System Diseases Commons, Neuroscience and Neurobiology Commons