SIRT3 mediates hippocampal synaptic adaptations to intermittent fasting and ameliorates deficits in APP mutant mice
Open accessAbstract
Intermittent food deprivation (fasting, IF) improves mood and cognition and protects neurons against excitotoxic degeneration in animal models of epilepsy and Alzheimer’s disease (AD). The mechanisms by which neuronal networks adapt to IF and how such adaptations impact neuropathological processes are unknown. We show that hippocampal neuronal networks adapt to IF by enhancing GABAergic tone, which is associated with reduced anxiety-like behaviors and improved hippocampus-dependent memory. These neuronal network and behavioral adaptations require the mitochondrial protein deacetylase SIRT3 as they are abolished in SIRT3-deficient mice and wild type mice in which SIRT3 is selectively depleted from hippocampal neurons. In the AppNL-G-F mouse model of AD, IF reduces neuronal network hyperexcitability and ameliorates deficits in hippocampal synaptic plasticity in a SIRT3-dependent manner. These findings demonstrate a role for a mitochondrial protein deacetylase in hippocampal neurons in behavioral and GABAergic synaptic adaptations to IF.
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In neurons, SIRT3 mediates adaptive responses to exercise, intermittent fasting, and excitatory challenges and helps prevent noise-induced hearing loss and spiral ganglia neurite degeneration.
“In neurons, SIRT3 mediates the adaptive responses of neurons to exercise, intermittent fasting, and excitatory challenges and helps prevent noise-induced hearing loss and spiral ganglia neurite degeneration (Brown et al., 2014; Cheng et al., 2016; Liu et al., 2019).”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Liu et al., 2019
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References 64 · Cited by 176
Research works printed but not linked: 1
- [42]Mattson MP An evolutionary perspective on why food overconsumption impairs cognition Trends Cogn. Sci. 2019 23 200 212 10.1016/j.tics.2019.01.003 30670325 PMC6412136 · DOI
- Authors
- Liu, Y., Cheng, A., Li, Y.-J., Yang, Y., Kishimoto, Y., Zhang, S., Wang, Y., Wan, R., Raefsky, S. M., Lu, D., Saito, T., Saido, T., Zhu, J., Wu, L.-J., & Mattson, M. P.
- Affiliations
- Mayo Clinic (US)
- National Institute on Aging (US)
- RIKEN Center for Brain Science (JP)
- Lieber Institute for Brain Development (US)
- Johns Hopkins University (US)
- Corresponding author
- Liu, Yong
- Mattson, Mark P.
- ORCID
- Venue
- Nature Communications
- Published
- 2019-04-23
- Volume
- 10
- Issue
- 1
- Pages
- 1886-1886
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6478744
- OpenAlex
- W2941209113
- Cited by
- 176
- References
- 64
- Citations by year
- 2026: 16 · 2025: 16 · 2024: 22 · 2023: 31 · 2022: 27 · 2021: 27 · 2020: 28 · 2019: 9
- FWCI
- 15.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute on Aging
- National Cancer Institute
- Topics
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- SIRT3, intermittent fasting, hippocampus, GABAergic inhibition, synaptic plasticity, Alzheimer's disease, AppNL-G-F mice, mitochondrial deacetylase, anxiety-like behavior, hippocampal-dependent memory, food deprivation
- MeSH terms
- Cortical Excitability, Superoxide Dismutase 2, Alzheimer Disease, Animals, Behavior, Animal, Cognition, Disease Models, Animal, Fasting, Hippocampus, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Mitochondria, Nerve Net, Neuronal Plasticity, Superoxide Dismutase, Amyloid beta-Protein Precursor, Oxidative Stress, Mice, Sirtuin 3, GABAergic Neurons
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