Subcategory: Social Sciences/Psychology/Economics
Room: Exhibit Hall
Kieran Andrew - Arizona State University
Co-Author(s): Veronica L Peña, Arizona State University, Tempe, Arizona; Shefali Prakash, Arizona State University, Tempe, Arizona; Haidyn L Bulen, Arizona State University, Australia; Steven Northup-Smith, Arizona State University, Tempe, Arizona; Charlotte Barker, Arizona State University, Tempe, Arizona; Victoria E Bernaud, Arizona State University, Tempe, Arizona; Alesia V Prakapenka, Arizona State University, Tempe, Arizona; Heather A Bimonte-Nelson, Arizona State University, Tempe, Arizona; Camryn Lizik, Arizona State University, Tempe, Arizona.
Approximately six million Americans have Alzheimer’s Disease (AD), characterized by degeneration of limbic and neocortex brain systems, development of yielding eventual severe cognitive impairment. While AD-associated neurodegeneration is still under study, accumulation of beta-amyloid plaques and neurofibrillary tangles are hallmarks of AD. Only after decades of pathological progression does clinical symptomatology begin to present in patients with probable AD. Currently, there is no available treatment that slows disease progression; animal models can increase our understanding of AD-related pathology and cognitive changes. Recently, a transgenic (TG) rat model of AD, the TgF344-AD, has been developed. This model expresses the mutant human amyloid precursor protein (APPSW) and presenilin 1 (PS1E9) genes, and includes amyloid beta plaque-like pathology, tau-like pathology, and neuronal loss. The current project utilizes the TG rat model to systematically assess spatial working and reference memory using the water radial arm maze (WRAM) in males and females with or without gonadectomy (the surgical removal of the gonads, GDX). Moreover, we analyzed our data using a novel method to examine detailed navigational strategies, focusing on the precise location in which errors were made relative to the correct choice: near misses or far-away misses relative to the remaining correct spatial locations. Eight groups were utilized in this study. Male and female TG and Wild Type rats received either GDX or Sham surgery, followed by WRAM testing. Female TG rats tended to show an overall impairment in spatial navigation, with significant impairment when working memory load was highly taxed. They also demonstrated impaired spatial accuracy for all distances of errors with a high demand working memory load, with a broader impairment (not specific to trial) for far-away errors, as compared to WT rat counterparts. For male rats, a Genotype x Treatment interaction for total errors was present. Notably, there was a Genotype effect for GDX rats, while in Sham rats there was no Genotype effect. This effect was especially prominent when working memory load was highly taxed. For male WT rats, only GDX improved spatial navigation; there was no cognitive difference between Sham treatment groups. Male TG rats demonstrated impaired spatial accuracy for near-miss errors when working load was highly taxed, and there were no effects in females. There was also a Genotype x Treatment interaction for male rats for errors that were far-away from the correct platform location; for GDX, male TG rats had impaired spatial accuracy, there was no difference between genotypes for Sham rats. Again, effects were prominent when working memory load was highly taxed. For male WT rats, GDX tended to improve spatial accuracy, while for male TG rats, Sham rats had better spatial accuracy. This pattern was also present on the highest working memory load. Overall, under the current experimental parameters, our results suggest that males are especially sensitive to gonadal hormone loss in young adulthood with near misses and far-away errors both accounting for patterns in performance. Analysis of brain pathology is currently underway to enhance understanding of the relationships between AD pathology, cognition, and hormone deprivation.
Funder Acknowledgement(s): This work was supported by the state of Arizona; the Arizona Department of Health Services [ADHS 14-052688]; the National Institute on Aging [AG028084]; and the NIH Arizona Alzheimer’s Disease Core Center [P30AG019610], [P30AG072980].
Faculty Advisor: Heather Bimonte-Nelson, email@example.com
Role: I performed the data scoring and entering for this project. Post Behavior in the WRAM, the performance of the rats needed to be scored for further analysis. This involved going back over the scoring sheet and counting the number of errors per trial, and double checking this scoring. After this was complete, I also entered the data into a spreadsheet for Data analysis.