Award Date

8-1-2018

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Psychology

First Committee Member

Jefferson Kinney

Second Committee Member

Rochelle Hines

Third Committee Member

James Hyman

Fourth Committee Member

Merrill Landers

Number of Pages

113

Abstract

Obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome are related disorders with wide-ranging and devastating effects that can be observed throughout the body. One important and understudied organ of damage is the brain. Clinical and epidemiological studies have found that T2DM, and more specifically hyperinsulinemia, significantly increases the risk of cognitive decline and increases the likelihood of Alzheimer’s disease (AD) and other forms of dementia in the elderly. Insulin has slightly different functions in the peripheral body than in the central nervous system and the dysregulation of these functions may contribute to the onset and progression of late-life neurodegenerative disease. These experiments were designed to investigate cognitive function and AD-related disease pathology in two different models of diabetes, one model resulting from a diabetogenic compound that selectively targets insulin-producing pancreatic β-cells and the other model based on diet-induced obesity. Additionally, these diabetic models were combined with a genetic mouse model of inflammation to explore the compounding effects of multiple AD risk factors. We found that diabetic-status, regardless of whether it was drug- or diet-induced, resulted in profound impairments in learning and memory and subtle alterations to AD-related histopathology within the hippocampus. Additionally, impairments were most dramatic in male mice; whereas females appeared to be more resistant to metabolic disturbances.

Keywords

Alzheimer's Disease; Dementia; Diabetes Mellitus; Inflammation; Insulin; Obesity

Disciplines

Medical Neurobiology | Neuroscience and Neurobiology | Neurosciences

File Format

pdf

Degree Grantor

University of Nevada, Las Vegas

Language

English

Rights

IN COPYRIGHT. For more information about this rights statement, please visit http://rightsstatements.org/vocab/InC/1.0/

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