SIRT3 mediates hippocampal synaptic adaptations to intermittent fasting and ameliorates deficits in APP mutant mice

Yong Liu, Aiwu Cheng, Yu Jiao Li, Ying Yang, Yuki Kishimoto, Shi Zhang, Yue Wang, Ruiqian Wan, Sophia M. Raefsky, Daoyuan Lu, Takashi Saito, Takaomi Saido, Jian Zhu, Long Jun Wu, Mark P. Mattson

Research output: Contribution to journalArticle

23 Scopus citations

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 App NL-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.

Original languageEnglish (US)
Article number1886
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    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. (2019). SIRT3 mediates hippocampal synaptic adaptations to intermittent fasting and ameliorates deficits in APP mutant mice. Nature communications, 10(1), [1886]. https://doi.org/10.1038/s41467-019-09897-1