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Induction of Atherosclerotic Plaques Through Activation of Mineralocorticoid Receptors in Apolipoprotein E-deficient Mice
Published on: September 26, 2018
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Ketones improves Apolipoprotein E4-related memory deficiency via sirtuin 3
Junxiang Yin1, Megan Nielsen1,2, Shiping Li1,3
1Barrow Neurological Institute, St. Joseph Hospital and Medical Center, Dignity Health Organization, Phoenix, AZ 85013, USA.
Aging
|July 8, 2019
Summary
Ketones enhance learning and memory in ApoE4 mice by boosting Sirt3 and neuronal energy metabolism. This suggests a potential therapeutic role for ketones in Alzheimer's disease prevention and treatment.
Area of Science:
- Neuroscience
- Metabolic Disorders
- Genetics
Background:
- Apolipoprotein E4 (ApoE4) is a primary genetic risk factor for Alzheimer's disease (AD).
- ApoE4 carriers exhibit cerebral hypometabolism, an early indicator of AD.
- Previous research linked ketone bodies to improved mitochondrial energy metabolism via sirtuin 3 (Sirt3).
Purpose of the Study:
- To investigate if ketones upregulate Sirt3 and ameliorate learning and memory deficits in ApoE4 mice.
- To explore the neuroprotective mechanisms of ketones in the context of ApoE4-associated cognitive decline.
Main Methods:
- Human ApoE3 and ApoE4 transgenic mice received daily subcutaneous injections of ketones (beta-hydroxybutyrate and acetoacetate) or saline for 3 months.
- Cognitive function was assessed using learning and memory tests.
- Sirt3 protein, synaptic markers (PSD95, Synaptophysin), NAD+/NADH ratio, and ATP levels were quantified in brain tissues.
Main Results:
- Ketone treatment significantly improved learning and memory in ApoE4 mice, but not in ApoE3 mice.
- Sirt3 levels, synaptic protein expression, NAD+/NADH ratio, and ATP production were notably increased in the hippocampus and cortex of treated ApoE4 mice.
- These findings indicate enhanced neuronal energy metabolism.
Conclusions:
- Ketones show potential in improving cognitive function in ApoE4 transgenic mice.
- Sirt3 appears to mediate the neuroprotective effects of ketones by enhancing neuronal energy metabolism.
- This study supports Sirt3's role in the potential prevention and treatment of Alzheimer's disease.
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