The impact of mild episodic ketosis on microglia and hippocampal long-term depression in 5xFAD mice
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ABSTRACT:
PROVIDER: PRJNA1122134 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29342648_1.fastq.gz | Fastqsanger.gz | |||
| SRR29342648_2.fastq.gz | Fastqsanger.gz | |||
| SRR29342649_1.fastq.gz | Fastqsanger.gz | |||
| SRR29342649_2.fastq.gz | Fastqsanger.gz | |||
| SRR29342650_1.fastq.gz | Fastqsanger.gz |
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Project description: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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