Cited by 541Sirtuins and Resveratrol in MedicineNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

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SIRT1 Is Essential for Normal Cognitive Function and Synaptic Plasticity

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Michan, S., Li, Y., Chou, M. M.-H., Parrella, E., Ge, H., Long, J. M., Allard, J. S., Lewis, K., Miller, M., Xu, W., Mervis, R. F., Chen, J., Guerin, K. I., Smith, L. E. H., McBurney, M. W., Sinclair, D. A., Baudry, M., de Cabo, R., Longo, V. D.·2010·Journal of Neuroscience

DOI 10.1523/jneurosci.0027-10.2010PMC PMC2921958

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Abstract

Conservation of normal cognitive functions relies on the proper performance of the nervous system at the cellular and molecular level. The mammalian nicotinamide-adenine dinucleotide-dependent deacetylase SIRT1 impacts different processes potentially involved in the maintenance of brain integrity, such as chromatin remodeling, DNA repair, cell survival, and neurogenesis. Here we show that SIRT1 is expressed in neurons of the hippocampus, a key structure in learning and memory. Using a combination of behavioral and electrophysiological paradigms, we analyzed the effects of SIRT1 deficiency and overexpression on mouse learning and memory as well as on synaptic plasticity. We demonstrated that the absence of SIRT1 impaired cognitive abilities, including immediate memory, classical conditioning, and spatial learning. In addition, we found that the cognitive deficits in SIRT1 knock-out (KO) mice were associated with defects in synaptic plasticity without alterations in basal synaptic transmission or NMDA receptor function. Brains of SIRT1-KO mice exhibited normal morphology and dendritic spine structure but displayed a decrease in dendritic branching, branch length, and complexity of neuronal dendritic arbors. Also, a decrease in extracellular signal-regulated kinase 1/2 phosphorylation and altered expression of hippocampal genes involved in synaptic function, lipid metabolism, and myelination were detected in SIRT1-KO mice. In contrast, mice with high levels of SIRT1 expression in brain exhibited regular synaptic plasticity and memory. We conclude that SIRT1 is indispensable for normal learning, memory, and synaptic plasticity in mice.

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Authors: Michan, S., Li, Y., Chou, M. M.-H., Parrella, E., Ge, H., Long, J. M., Allard, J. S., Lewis, K., Miller, M., Xu, W., Mervis, R. F., Chen, J., Guerin, K. I., Smith, L. E. H., McBurney, M. W., Sinclair, D. A., Baudry, M., de Cabo, R., & Longo, V. D.
Affiliations: University of Southern California (US)
National Institutes of Health (US)
University of South Florida (US)
Harvard University (US)
University of Ottawa (CA)
ORCID: Parrella, E.
Lewis, K.
Miller, M.
Xu, W.
Smith, L. E. H.
McBurney, M. W.
Sinclair, D. A.
Baudry, M.
Longo, V. D.
Venue: Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2010-07-21
Volume: 30
Issue: 29
Pages: 9695-9707
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.0027-10.2010
PMC: PMC2921958
OpenAlex: W2075043109
Cited by: 541
References: 77
Citations by year: 2026: 26 · 2025: 29 · 2024: 31 · 2023: 29 · 2022: 51 · 2021: 63 · 2020: 36 · 2019: 26 · 2018: 41 · 2017: 35 · 2016: 26 · 2015: 28 · 2014: 31 · 2013: 32 · 2012: 24
FWCI: 11.23
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Neuroscience (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
Funders: Ellison Medical Foundation
Glenn Foundation for Medical Research
University of Southern California
Fondation pour la Recherche Médicale
National Institutes of Health
Manton Center for Orphan Disease Research, Boston Children's Hospital
Canadian Institutes of Health Research
National Institute on Aging (K01AG001028, P01AG027916, R01AG028730, R01AG019719)
National Eye Institute (EY017017, EY017017 04S1, R01EY017017)
National Institute of Neurological Disorders and Stroke
Topics: Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: SIRT1, cognitive function, learning and memory, synaptic plasticity, hippocampus, dendritic spine morphology, dendritic branching, ERK1/2 phosphorylation, lipid metabolism, myelination, NMDA receptor, classical conditioning, spatial learning, immediate memory, SIRT1 knockout mice
MeSH terms: Animals, Cognition, Gene Expression Regulation, Hippocampus, Learning, Memory, Neurons, Tissue Distribution, Long-Term Potentiation, Mice, Knockout, Patch-Clamp Techniques, Dendritic Spines, Mice, Sirtuin 1

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SIRT1 Is Essential for Normal Cognitive Function and Synaptic Plasticity

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