Faculty Articles
Document Type
Article
Publication Date
8-9-2023
Publication Title
Biology of Sex Differences
Volume
14
Issue/Number
51
ISSN
2042-6410
Abstract/Excerpt
BACKGROUND: Alzheimer's disease (AD) is notably associated with cognitive decline resulting from 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 several years prior to the onset of cognitive symptoms. Therefore, altered metabolic processes may serve as a biomarker for AD, as well as a target for treatment, considering they are likely both a result of pathological changes and contributor to disease progression. Previously, we reported sexually dimorphic metabolic disturbances in ~ 7-month-old 3xTg-AD mice, accompanied by differences in systemic and hypothalamic inflammation.
METHODS: 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 differences emerge.
RESULTS: In agreement with our previous study, AD males displayed less weight gain and adiposity, as well as reduced blood glucose levels following a glucose challenge, compared to females. These trends were apparent by 6-9 months of age, coinciding with increased expression of inflammatory markers (Iba1, GFAP, TNF-α, and IL-1β) in the hypothalamus of AD males.
CONCLUSIONS: These findings provide additional evidence for sex-dependent effects of AD pathology on energy and glucose homeostasis, which may be linked to hypothalamic inflammation.
DOI
10.1186/s13293-023-00536-5
ORCID ID
0000-0002-5110-9183
PubMed ID
37559092
NSUWorks Citation
Robison, L. S.,
Gannon, O. J.,
Salinero, A. E.,
Abi-Ghanem, C.,
Kelly, R. D.,
Riccio, D. A.,
Mansour, F. M.,
Zuloaga, K. L.
(2023). Sex differences in metabolic phenotype and hypothalamic inflammation in the 3xTg-AD mouse model of Alzheimer's disease.. Biology of Sex Differences, 14(51).
Available at: https://nsuworks.nova.edu/cps_facarticles/2037
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Comments
Acknowledgements Thank you to Nathan Albert, Melissa Thomas, Alvira Tyagi, and Allegra Wu for assistance with tissue collection.
Funding This work was funded by NINDS F31 NS115290 (OJG), NINDS/NIA R01NS110749 (KLZ), NIA U01AG072464 (KLZ), Albany Medical College startup funds, American Heart Association 946666 (LSR), NINDS R16NS134540-01 (LSR), NIA R03AG081865-01 (LSR).
© The Author(s) 2023.