SIRT3 mediates hippocampal synaptic adaptations to intermittent fasting and ameliorates deficits in APP mutant mice
Liu Y, Cheng A, Li YJ, Yang Y, Kishimoto Y, Zhang S, Wang Y, Wan R, Raefsky SM, Lu D, Saito T, Saido T, Zhu J, Wu LJ, Mattson MP
Nature communications · 137 citations
How it was studied
- Design
- Animal study (classified by our AI screen)
- Studied in
- Animals
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- Government
- National Institute on Aging
- Government
- National Cancer Institute
Based on 2 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2019-04-23 · Nat Commun · vol. 10 · issue 1 · p. 1886
- Publisher
- Nature Portfolio
- Cited
- 177 citations · more than 99% of similar papers · 11.4× the field average
- Impact
- Top 10% most cited in its field
- References
- 65 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Dietary Effects on Health · Biochemical effects in animals · Diet and metabolism studies
- Keywords
- Hippocampal formation, Neuroscience, SIRT3, Synaptic plasticity, GABAergic, Hippocampus, Biology, Sirtuin, Inhibitory postsynaptic potential, Receptor, Biochemistry
- MeSH
- hippocampus, nerve net, mitochondria, animals, mice, inbred c57bl, mice, transgenic, humans, mice, alzheimer disease, disease models, animal, superoxide dismutase, amyloid beta-protein precursor, fasting, behavior, animal, cognition, oxidative stress, neuronal plasticity, male, sirtuin 3, gabaergic neurons, cortical excitability, superoxide dismutase 2
15 authors
From US, CN, JP
- Yong Liu · correspondingMayo Clinic; Mayo Clinic in Arizona; Institute on Aging; National Institute on Aging; Mayo Clinic in Florida
- Aiwu ChengNational Institute on Aging
- Yu-Jiao LiMayo Clinic; WinnMed; Air Force Medical University
- Ying YangNational Institute on Aging
- Yuki KishimotoNational Institute on Aging
- Shi ZhangNational Institute on Aging
Abstract
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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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