Type

Text

Type

Dissertation

Advisor

Robinson, John K | Anderson, Brenda | Gerrig, Richard | VanNostrand, William.

Date

2015-12-01

Keywords

Alzheimer's disease, Cardiovascular exercise, Cognitive enrichment, Transgenic murine models | Neurosciences

Department

Department of Biopsychology.

Language

en_US

Source

This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.

Identifier

http://hdl.handle.net/11401/77007

Publisher

The Graduate School, Stony Brook University: Stony Brook, NY.

Format

application/pdf

Abstract

Despite numerous advances in our understanding of the mechanisms that underlie Alzheimer’s disease (AD), there is still no cure, and the disease continues to pose a severe public health problem. It has become clear that many factors, including certain lifestyle practices, may contribute to the development of the disease; however, much remains to be learned about how lifestyle factors may prevent or delay cognitive decline. Unlike human epidemiological studies, murine models can provide clearer inferences about causality. The present studies focus on two lifestyle factors: cognitive enrichment and cardio-vascular exercise. Specifically, the effects of lifestyle interventions on behavioral performance and pathology were studied in a transgenic murine model of vascular amyloid pathology, the Tg-SwDI. The vascular component of this model’s pathology is an important feature of AD pathology that shows particular promise for being responsive to these interventions. The first two studies examined the effects of a novel, progressive cognitive training intervention on pathology and behavior in three-month-old Tg-SwDI mice, as well as in a model of parenchymal amyloid (Tg-5xFAD mice). Only marginal improvements were observed in cognitive measures, without corresponding changes in gross or regional levels of amyloid pathology or in levels of regional neuroinflammation. These data do not support the value of isolated cognitive training regimens, though the feasibility of this approach in murine models is demonstrated. The final study examined the impact of four months of 1, 3, or 12-hours of voluntary cardiovascular exercise on cognitive-behavioral measures in three-month-old Tg-SwDI and healthy wild-type mice. Exercise effects were evident across multiple behavioral measures, but did not provide reliable improvement of performance across tests. Taken together, these results highlight the potential for differential susceptibility of particular features of AD to the effects of lifestyle. | Despite numerous advances in our understanding of the mechanisms that underlie Alzheimer’s disease (AD), there is still no cure, and the disease continues to pose a severe public health problem. It has become clear that many factors, including certain lifestyle practices, may contribute to the development of the disease; however, much remains to be learned about how lifestyle factors may prevent or delay cognitive decline. Unlike human epidemiological studies, murine models can provide clearer inferences about causality. The present studies focus on two lifestyle factors: cognitive enrichment and cardio-vascular exercise. Specifically, the effects of lifestyle interventions on behavioral performance and pathology were studied in a transgenic murine model of vascular amyloid pathology, the Tg-SwDI. The vascular component of this model’s pathology is an important feature of AD pathology that shows particular promise for being responsive to these interventions. The first two studies examined the effects of a novel, progressive cognitive training intervention on pathology and behavior in three-month-old Tg-SwDI mice, as well as in a model of parenchymal amyloid (Tg-5xFAD mice). Only marginal improvements were observed in cognitive measures, without corresponding changes in gross or regional levels of amyloid pathology or in levels of regional neuroinflammation. These data do not support the value of isolated cognitive training regimens, though the feasibility of this approach in murine models is demonstrated. The final study examined the impact of four months of 1, 3, or 12-hours of voluntary cardiovascular exercise on cognitive-behavioral measures in three-month-old Tg-SwDI and healthy wild-type mice. Exercise effects were evident across multiple behavioral measures, but did not provide reliable improvement of performance across tests. Taken together, these results highlight the potential for differential susceptibility of particular features of AD to the effects of lifestyle. | 163 pages

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