ArticleInternational journal of molecular sciences2020
A Dietary Ketone Ester Normalizes Abnormal Behavior in a Mouse Model of Alzheimer's Disease.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- Pharmacokinetic effects of a single dose nutritional ketone ester supplement on brain glucose and ketone metabolism in alcohol use disorder.Psychiatry research. Neuroimaging · 2026Trial
- Ketogenic diet enhances cognitive-behavioral function and hippocampal neurogenesis while attenuating amyloid pathology in Tg-SwDI mice.Journal of Alzheimer's disease : JAD · 2026Article
- Glycolysis: The Bridge Between Cellular Interaction and Alzheimer's Disease.Biomolecules · 2026Review
- Review
- Ketogenic Metabolism in Neurodegenerative Diseases: Mechanisms of Action and Therapeutic Potential.Metabolites · 2025Review
- Article
- Ketone ester-enriched diet ameliorates motor and dopamine release deficits in MitoPark mice.The European journal of neuroscience · 2024Article
- Molecular mechanisms of aging and anti-aging strategies.Cell communication and signaling : CCS · 2024Review
- Adenosine deficiency facilitates CA1 synaptic hyperexcitability in the presymptomatic phase of a knock in mouse model of Alzheimer's disease.bioRxiv : the preprint server for biology · 2024Article
- Ketogenic therapy towards precision medicine for brain diseases.Frontiers in nutrition · 2024Review
- Molecular Mechanisms of Neuroprotection by Ketone Bodies and Ketogenic Diet in Cerebral Ischemia and Neurodegenerative Diseases.International journal of molecular sciences · 2023Review
- (R,R)-BD-AcAc2 Mitigates Chronic Colitis in Rats: A Promising Multi-Pronged Approach Modulating Inflammasome Activity, Autophagy, and Pyroptosis.Pharmaceuticals (Basel, Switzerland) · 2023Article
- A Novel Ketone-Supplemented Diet Improves Recognition Memory and Hippocampal Mitochondrial Efficiency in Healthy Adult Mice.Metabolites · 2022Article
- Effects of Ketogenic Diet on Neuroinflammation in Neurodegenerative Diseases.Aging and disease · 2022Article
- Review
- The Metabolic Effects of Ketones.International journal of molecular sciences · 2021Article
- Ketogenic regimens for acute neurotraumatic events.Current opinion in biotechnology · 2021Review
- Beneficial Effects of Exogenous Ketogenic Supplements on Aging Processes and Age-Related Neurodegenerative Diseases.Nutrients · 2021Review
- Ketogenic diet reduces alcohol withdrawal symptoms in humans and alcohol intake in rodents.Science advances · 2021Article
- Can Ketogenic Diet Improve Alzheimer's Disease? Association With Anxiety, Depression, and Glutamate System.Frontiers in nutrition · 2021Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Because of a decreased sensitivity toward insulin, a key regulator of pyruvate dehydrogenase (PDH), Alzheimer's patients have lower brain glucose utilization with reductions in Tricarboxylic Acid (TCA) cycle metabolites such as citrate, a precursor to n-acetyl-aspartate. In the 3xTgAd mouse model of Alzheimer's disease (AD), aging mice also demonstrate low brain glucose metabolism. Ketone metabolism can overcome PDH inhibition and restore TCA cycle metabolites, thereby enhancing amino acid biosynthesis. A ketone ester of d-β-hydroxybutyrate was incorporated into a diet (Ket) and fed to 3xTgAd mice. A control group was fed a calorically matched diet (Cho). At 15 months of age, the exploratory and avoidance-related behavior patterns of the mice were evaluated. At 16.5 months of age, the animals were euthanized, and their hippocampi were analyzed for citrate, α-ketoglutarate, and amino acids. In the hippocampi of the Ket-fed mice, there were higher concentrations of citrate and α-ketoglutarate as well as higher concentrations of glutamate, aspartate and n-acetyl-aspartate compared with controls. There were positive associations between (1) concentrations of aspartate and n-acetyl-aspartate (n = 14, R = 0.9327), and (2) α-ketoglutarate and glutamate (n = 14, R = 0.8521) in animals maintained on either diet. Hippocampal n-acetyl-aspartate predicted the outcome of several exploratory and avoidance-related behaviors. Ketosis restored citrate and α-ketoglutarate in the hippocampi of aging mice. Higher concentrations of n-acetyl-aspartate corresponded with greater exploratory activity and reduced avoidance-related behavior.
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