Faculty Proceedings, Presentations, Speeches and Lectures

Sex Differences in Metabolic and Hypothalamic Disturbances in the 3xTg-AD Mouse Model of Alzheimer’s Disease Across the Lifespan

Date Range

2021-11-08 to 2021-11-11

Event Location / Date(s)

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Presentation Date

11-11-2021

Document Type

Poster

Description

Alzheimer’s disease (AD) is often associated with cognitive decline and impaired function of hippocampal and cortical areas; however, several other domains and corresponding brain regions are affected. One such brain region is the hypothalamus, shown to atrophy and develop amyloid and tau pathology in AD patients. The hypothalamus controls several functions necessary for survival, including energy and glucose homeostasis. Changes in appetite and body weight are common in AD, often seen prior to the onset of cognitive symptoms. Therefore, altered metabolic processes may serve as a biomarker for AD and/or a target for treatment, considering they are likely both a result of and contributor to disease progression. Previously, we reported sex differences in metabolic disturbances in ~7-month-old 3xTg-AD mice, accompanied by systemic and hypothalamic inflammation. In the current study, we investigated metabolic outcomes and hypothalamic inflammation in 3xTg-AD males and females at 3, 6, 9, and 12 months of age to determine when these sex-specific metabolic phenotypes emerge. In agreement with our previous study, AD males displayed reduced weight gain and adiposity, as well as reduced blood glucose levels following a glucose challenge, compared to females by 6 months of age. Additionally, we note increased expression of inflammatory markers (Iba1, GFAP, TNF-a, and IL-1B) in the hypothalamus of AD males at 6-9 months. These findings provide additional evidence for sex-dependent effects of AD pathology on altered metabolism, which may be linked to hypothalamic inflammation.

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