Hunger in the Absence of Caloric Restriction Improves Cognition and Attenuates Alzheimer's Disease Pathology in a Mouse Model
Open accessAbstract
It has been shown that caloric restriction (CR) delays aging and possibly delays the development of Alzheimer's disease (AD). We conjecture that the mechanism may involve interoceptive cues, rather than reduced energy intake per se. We determined that hunger alone, induced by a ghrelin agonist, reduces AD pathology and improves cognition in the APP-SwDI mouse model of AD. Long-term treatment with a ghrelin agonist was sufficient to improve the performance in the water maze. The treatment also reduced levels of amyloid beta (Aβ) and inflammation (microglial activation) at 6 months of age compared to the control group, similar to the effect of CR. Thus, a hunger-inducing drug attenuates AD pathology, in the absence of CR, and the neuroendocrine aspects of hunger also prevent age-related cognitive decline.
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Activation of ghrelin signaling attenuates microglial activation in mouse models of normal aging, accelerated aging, and Alzheimer's disease.
“the activation of ghrelin signaling has been shown to attenuate microglial activation in mouse models of normal aging, accelerated aging and AD.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [557]
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Self-citation
- Authors
- Dhurandhar, E. J., Allison, D. B., van Groen, T., & Kadish, I.
- Affiliations
- University of Alabama at Birmingham (US)
- Corresponding author
- Kadish, Inga
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-04-02
- Volume
- 8
- Issue
- 4
- Pages
- e60437
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3614512
- OpenAlex
- W2027989695
- Cited by
- 79
- References
- 40
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 10 · 2022: 6 · 2021: 11 · 2020: 6 · 2019: 8 · 2018: 6 · 2017: 6 · 2016: 8 · 2015: 4 · 2014: 4 · 2013: 4
- FWCI
- 4.64
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Eli Lilly and Company
- National Institutes of Health (NS47466)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK062710, P30DK079626)
- National Institute of Neurological Disorders and Stroke (P30-NS47466, P30NS047466)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- hunger, caloric restriction, Alzheimer's disease, ghrelin agonists, amyloid-beta, microglial activation, neuroinflammation, cognitive decline, interoception, neuroendocrine signaling, aging
- MeSH terms
- Alzheimer Disease, Animals, Cognition, Disease Models, Animal, Hunger, Male, Mice, Inbred C57BL, Caloric Restriction, Mice, Ghrelin
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