Impact of Long-Term Dietary High Fat and Eicosapentaenoic Acid on Behavior and Hypothalamic-Pituitary-Adrenal Axis Activity in Amyloidogenic APPswe/PSEN1dE9 Mice
ORCID
Latha Ramalingam: 0000-0002-4856-7327
Document Type
Article
Date
2-2024
Keywords
Alzheimer’s disease, Behavior, Corticosterone, Diet-induced obesity, Eicosapentaenoic acid
Disciplines
Molecular, Genetic, and Biochemical Nutrition | Other Nutrition
Description/Abstract
Introduction: Alzheimer's disease (AD) alters neurocognitive and emotional function and causes dysregulation of multiple homeostatic processes. The leading AD framework pins amyloid beta plaques and tau tangles as primary drivers of dysfunction. However, many additional variables, including diet, stress, sex, age, and pain tolerance, interact in ways that are not fully understood to impact the onset and progression of AD pathophysiology. We asked: (1) does high-fat diet, compared to low-fat diet, exacerbate AD pathophysiology and behavioral decline? And, (2) can supplementation with eicosapentaenoic (EPA)-enriched fish oil prevent high-fat-diet-induced changes?
Methods: Male and female APPswePSdE9 mice, and their non-transgenic littermates, were randomly assigned to a diet condition (low-fat, high-fat, high-fat with EPA) and followed from 2 to 10 months of age. We assessed baseline corticosterone concentration during aging, pain tolerance, cognitive function, stress coping, and corticosterone response to a stressor.
Results: Transgenic mice were consistently more active than non-transgenic mice but did not perform worse on either cognitive task, even though we recently reported that these same transgenic mice exhibited metabolic changes and had increased amyloid beta. Mice fed high-fat diet had higher baseline and post-stressor corticosterone, but diet did not impact cognition or pain tolerance. Sex had the biggest influence, as female mice were consistently more active and had higher corticosterone than males.
Conclusion: Overall, diet, genotype, and sex did not have consistent impacts on outcomes. We found little support for predicted interactions and correlations, suggesting diet impacts metabolic function and amyloid beta levels, but these outcomes do not translate to changes in behaviors measured here.
Recommended Citation
Harris BN, Yavari M, Ramalingam L, Mounce PL, Alers Maldonado K, Chavira AC, Thomas S, Scoggin S, Biltz C, Moustaid-Moussa N. Impact of Long-Term Dietary High Fat and Eicosapentaenoic Acid on Behavior and Hypothalamic-Pituitary-Adrenal Axis Activity in Amyloidogenic APPswe/PSEN1dE9 Mice. Neuroendocrinology. 2024;114(6):553-576. doi: 10.1159/000536586. Epub 2024 Feb 1. PubMed PMID: 38301617; PubMed Central PMCID: PMC11153005.
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This work is licensed under a Creative Commons Attribution 4.0 International License.
