ArticleFASEB bioAdvances2024
The impact of mild episodic ketosis on microglia and hippocampal long-term depression in 5xFAD mice.
Article in FASEB bioAdvances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- β-hydroxybutyrate regulates microglia M1/M2 polarization and phagocytosis through the JAK1/STAT1 pathway to reduce neuroinflammation and exert anti-epileptic effects.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- A ketogenic diet improves memory in females in the APOE4 mouse model of Alzheimer's disease.GeroScience · 2026Article
- Microglia Mitochondrial Metabolism in Neurological Diseases.Molecular neurobiology · 2026Review
- Abnormalities of lipid metabolism in the progression and treatment of depression.Frontiers in psychiatry · 2025Review
- Beta-hydroxybutyrate (BHB) elicits concentration-dependent anti-inflammatory effects on microglial cells which are reversible by blocking its monocarboxylate (MCT) importer.Frontiers in aging · 2025Article
- The impact of mild episodic ketosis on microglia and hippocampal long-term depression in 5xFAD mice.FASEB bioAdvances · 2024Article
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Authors and funding
4 authors.
Funding
Abstract
Ketotherapeutics is a potential metabolic intervention for mitigating dementias; however, its mechanisms and optimal methods of application are not well understood. Our previous in vitro study showed that β-hydroxybutyrate (BHB), a major ketone body, reverses pathological features of amyloid-β oligomer (AβO)-activated microglia. Here we tested the in vivo effects of BHB on microglia and synaptic plasticity in the 5xFAD Alzheimer's disease (AD) mouse model. A short 1-week regimen of daily intraperitoneal injection of BHB (250 mg/kg), which induced brief and mild daily episodic ketosis, was sufficient to mitigate pro-inflammatory microglia activation and reduce brain amyloid-β deposition by enhancing phagocytosis. Remarkably, it mitigated the deficits of hippocampal long-term depression but not long-term potentiation, and this effect was linked to suppression of NLRP3 inflammasome-generated IL-1β. As ketogenic diets are known for poor compliance, our study opens the possibility for alternative approaches such as short-term BHB injections or dietary ketone esters that are less restrictive, potentially safer, and easier for compliance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.